Monday, November 30, 2009

S-methylmethionine (Vitamin U) as antiulcer agent .......

About S-methylthionine :

S-Methylmethionine, or S-methyl-L-methionine, is a derivative of methionine In plants, it is produced from methionine by the enzyme methionine S-methyltransferase. S-Methyl- methionine is sometimes called vitamin U in naturopathic medicine, but it is not recognized as a vitamin by mainstream nutrition science. Methionine in itself has not been demonstrated as effective for treating peptic and duodenal ulcers. Its proponents claim that sources of methionine are limited, or claim it can be found only in raw cabbage; however, these claims are incorrect. Methionine is a common amino acid found in a wide variety of fruits, vegetables, and legumes.

More interesting results by the researchers from the Stanford University, have further substantiated the claim that it can be used to treat peptic and duodenal ulcers.

Acetaminophen is a pain reliever present in many over-the-counter cold and flu medicines. It is broken down, or metabolized, in the body into byproducts , one of which can be very toxic to the liver. At normal, therapeutic levels, this byproduct is easily deactivated when it binds to a naturally occurring, protective molecule called glutathione. But the body's glutathione stores are finite, and are quickly depleted when the recommended doses of acetaminophen are exceeded. Acetaminophen overdose is the most common cause of liver transplantation and the only effective antidote is an unpalatable compound called NAC that can induce nausea and vomiting, and must be administered as soon as possible after the overdose.

As per the claim by the authors, an enzyme called Bhmt2 helped to generate more glutathione. Bhmt2 works by converting the diet-derived molecule S-methylmethionine, or SMM, into methionine, which is subsequently converted in a series of steps into glutathione. The researchers confirmed the importance of the pathway by showing that SMM conferred protection against acetaminophen-induced liver toxicity only in strains of mice in which the Bhmt2 pathway was functional.

By administering SMM, which is found in every flowering plant and vegetable, we were able to prevent a lot of the drug’s toxic effect,” said Peltz. He and his colleagues are now working to set up clinical trials at Stanford to see whether it will have a similar effect in humans. In the meantime, though, he cautions against assuming that dosing oneself with SMM will protect against acetaminophen overdose....

Source : http://med.stanford.edu/ism/2009/november/peltz.html

Sunday, November 29, 2009

Top 10 Amazing Chemistry Videos

Top 10 Amazing Chemistry Videos

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Mode of action of tetrathiomolybdate (a drug for Wilson's disaese) established ?

We know that Ammonium tetrathiomolybdate ([NH4]2MoS4), was first used therapeutically in the treatment of copper toxicosis in animals. It was then introduced as a treatment in Wilson's disease, a hereditary copper metabolism disorder, in humans; it acts both by competing with copper absorption in the bowel and by increasing excretion. It has also been found to have an inhibitory effect on angiogenesis, potentially via the inhibition of Cu ion dependent membrane translocation process invovling a non-classical secretion pathway. This makes it an interesting investigatory treatment for cancer, age-related macular degeneration, and other diseases featuring excessive blood vessel deposition. Though the activity was established mode of action was to be established. Now researchers from Northwestern University , have achieved something which was eluding so for. As per the claim by the researchers, the three-dimensional structure of TM bound to copper-loaded metallochaperones. The drug sequesters the chaperone and its bound copper, preventing both from carrying out their normal functions in the cell. For patients with Wilson disease and certain cancers whose initial growth is helped by copper-dependent angiogenesis, this is very promising. O'Halloran and his research team studied the copper chaperone protein Atx1, which provides a good model of copper metabolism in animal cells.

The drug brings three copper chaperones into close quarters, weaving them together through an intricate metal-sulfur cluster in a manner that essentially shuts down the copper ferrying system.

The nest-shaped structure of the metal-sulfur cluster discovered by the researchers was completely unanticipated. The sulfur atoms in the tetrathiomolybdate bound to the copper atoms to form an open cluster that bridged the chaperone proteins. In this manner, three copper proteins were jammed onto one thiomolybdate. More interestingly the structure of the complex has been concluded by X-ray studies. Based on the structure and additional experiments, the scientists propose that the drug inhibits the traffic of copper within the cell because of its ability to sequester copper chaperones and their cargo in clusters, rendering the copper inactive.

Copper also is an important cofactor for tumor angiogenesis, the process of growing new blood vessels to feed the tumor. Researchers believe this is why tetrathiomolybdate has shown promise as an anti-cancer drug. Hope the clinical trials (phase II) of tetrathiomolybdate (as anticancer drug) a success and wide applications of this drug (as amyotrophic lateral sclerosis (ALS), Parkinson's disease, multiple sclerosis and Alzheimer's disease, primary pulmonary hypertension and left ventricular hypertrophy) will help patients to breathe a sigh of relief...

Ref : http://www.northwestern.edu/newscenter/stories/2009/11/crystal.html

Saturday, November 28, 2009

Palmitoylethanolamide - a natural body fat as antiinflammatory agent !

About Palmitoylethanolamide : Palmitoylethanolamide, is an endogenous fatty acid amide which has been demonstrated to bind to peroxisome proliferator-activated receptor alpha (PPAR-α) , GPR55 and GPR119. PEA has been shown to have anti-inflammatory and anti-nociceptive properties. PEA is metabolized by fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing acid amidase (NAAA), the latter of which has more specificity towards PEA over other fatty acid amides.

For decades, it has been known that palmitoylethanolamide (PEA), is a potent anti-inflammatory substance that reduces both allergic symptoms and occurrences of rheumatic fever, but researchers understood little about how PEA works. But now Daniele Piomelli, the Louise Turner Arnold (Chair in Neurosciences at UCI), and colleagues found that levels of PEA are tightly regulated by immune system cells. In turn, PEA helps control the activity of these cells, which are called into action to fight infection, disease and injury in the body. In addition, they found that PEA - also present in foods like eggs and peanuts , is deactivated by a protein called N-acylethanolamine-hydrolyzing acid amidase, which is an enzyme that breaks down molecules controlling cell inflammation.

When given to rodents, the compound increased the levels of PEA in their immune cells and reduced the amount of inflammation elicited by an inflammatory substance. Furthermore, when administered to the spinal cords of mice after spinal cord injury, the compound decreased inflammation associated with the trauma and improved the recovery of motor function.

As most of the antiinflammatory drugs available these days have side effects, this drug may be a boon to the sufferers....

Ref : http://today.uci.edu/news/nr_PEA_091116.php

Generating electricity from air flow

A group of researchers at the City College of New York is developing a new way to generate power for planes and automobiles based on materials known as piezoelectrics, which convert the kinetic energy of motion into electricity


Details ..........Generating electricity from air flow

siRNA for pachyonychia congenita treatment...

In continuation of my update on siRNAs, I found this recent development an interesting finding in the field of RNAi class of compounds. Dr. Sancy Leachman and co workers found that siRNA derivative can be a new treatment for pachyonychia congenita, an ultra-rare genetic skin condition caused by mutations in a gene called keratin.

As per the claim by the authors, siRNA, works by preventing the gene with the mutation from being expressed but permitting the healthy keratin genes to function normally. The study marked the first time that the skin of a human subject was treated with this type of drug. Researchers say that in this single patient trial the drug worked, had no serious side effects, and has vast potential because of its ability to specifically and potently target single molecules, making it an option for many other genetic diseases, including cancer.

The patient was treated with siRNA on her right foot and with placebo on the left foot. The callus on the right foot that received the siRNA fell off at the site of injection, but this did not happen on the left foot. Congrats for this remarkable achievement...

Source : http://healthcare.utah.edu/dermatology/about/faculty/sancyleachman.html

Friday, November 27, 2009

Molecule discovered that makes obese people develop diabetes

Molecule discovered that makes obese people develop diabetes

New Drug Application for Tramadol....


About Tramadol :

Tramadol is a centrally acting analgesic, used for treating moderate to severe pain. Tramadol was developed by the German pharmaceutical company Grünenthal GmbH in the late 1970.

Tramadol possesses agonist actions at the μ-opioid receptor and affects reuptake at the noradrenergic and serotonergic systems. Tramadol is a compound with mild and delayed μ-agonist activity.

Tramadol is a synthetic stripped-down analog of Codeine and, as such, is an opioid. The opioid agonistic effect of tramadol and its major metabolite(s) almost exclusively effects the μ-opioid receptor. This characteristic is notable, because even morphine is not exclusive to the μ-receptor, although it manifests the preponderance of its opioid agonistic effects here. Tramadol is used to treat moderate to moderately severe pain and most types of neuralgia, including trigeminal neuralgia.

Recently, Par Pharmaceutical Companies, Inc received FDA approval for the abbreviated New Drug Application for the 100mg and 200mg strengths of tramadol ER.....

Source : http://www.parpharm.com/media/NR_20091116.jsp

Wednesday, November 25, 2009

Oncolytics Biotech's REOLYSIN combined with paclitaxel and carboplatin well tolerated for advanced cancers

In continuation of my follow up on cisplatin derivatives, I find this article interesting to share with.....

Oncolytics Biotech's REOLYSIN combined with paclitaxel and carboplatin well tolerated for advanced cancers

Green tea prevents the development of hepatic fibrosis in rat model of DMN-induced liver fibrosis

Green tea prevents the development of hepatic fibrosis in rat model of DMN-induced liver fibrosis

Nicardipine Hydrochloride injection is back !

About Nicardipine :

We know that Nicardipine hydrochloride (Cardene) is a medication used to treat high blood pressure and angina. It belongs to the class of calcium channel blockers.

Nicardipine is a dihydropyridine calcium-channel blocking agent used for the treatment of vascular disorders such as chronic stable angina, hypertension, and Raynaud's phenomenon. It is available in oral and intravenous formulations. Its mechanism of action and clinical effects closely resemble those of nifedipine and the other dihydropyridines (amlodipine, felodipine), except that nicardipine is more selective for cerebral and coronary blood vessels. Furthermore, nicardipine does not intrinsically decrease myocardial contractility and may be useful in the management of congestive heart failure. Nicardipine also has a longer half-life than nifedipine. Nicardipine was approved by the FDA in December 1988. The patent for both Cardene and Cardene SR expired in October 1995.

Recently, Caraco Pharmaceutical Laboratories, Ltd. has launched Nicardipine Hydrochloride Injection immediately following Sun Pharma's final approval from the US Food and Drug Administration (FDA).

Nicardipine Hydrochloride Injection is indicated for the short-term treatment of hypertension when oral therapy is not feasible or not desirable. These Nicardipine Hydrochloride Injections are available as 25 mg/10ml single use ampuls containing 2.5 mg/ml of the drug....

Source : http://phx.corporate-ir.net/phoenix.zhtml?c=98920&p=irol-newsArticle_Print&ID=1356898&highlight=


Tuesday, November 24, 2009

Vardenafil (PDE5 inhibitor) as antiulcer agent?


Vardenafil, (Levitra, Bayer) is a PDE5 inhibitor used for treating impotence (erectile dysfunction). Vardenafil's indications and contra-indications are the same as with other PDE5 inhibitors; it is closely related in function to sildenafil citrate (Viagra) and tadalafil (Cialis). Structurally, the difference between the vardenafil molecule and sildenafil citrate is a nitrogen atom's position and the change of sildenafil's piperazine ring methyl group to an ethyl group. Tadalafil is structurally different from both sildenafil and vardenafil. Vardenafil's relatively short effective time is comparable to but somewhat longer than sildenafil's.

We know that most of the NSAIDs are associated with ulcerogenecity. Though there are many compounds with different mode of action have been tested (and some of them are being used) to treat the peptic ulcer, compounds with phosphodiesterase 5 inhibitor were not tested before Dr. Karakaya of Zonguldak Karaelmas University-who have reported that Vardenafil can be used to treat the NSAID-induced gastric ulcer. As per the claim by the researchers the activity is dose dependent.

Ref : http://www.wjgnet.com/1007-9327/abstract_en.asp?f=5091&v=15

Monday, November 23, 2009

Spineology's Capture Facet Screw System receives FDA clearance

Spineology's Capture Facet Screw System receives FDA clearance

A potassium channel blocker to restore nerve function in patients with spinal cord injuries..

The experimental compound, 4-aminopyridine-3-methyl hydroxide, has been shown to restore function to damaged axons, slender fibers that extend from nerve cells and transmit electrical impulses in the spinal cord.

The researchers subjected spinal cord tissue to stresses that mimic what happens in a compression injury, which stretches nerves. Then they treated the damaged axons with 4-aminopyridine-3-methyl hydroxide. The same drug is used primarily as a research tool and also to manage symptoms of multiple sclerosis.

The axons of each nerve are sheathed in a thick insulating lipid layer, called myelin, which enables the transmission of signals without short circuiting, much like the insulation surrounding electrical wires. Spinal cord trauma damages the myelin sheath, exposing "fast potassium channels" that are embedded in the axons and are critical for transmitting nerve impulses.

The researchers also discovered that 4-aminopyridine-3-methyl hydroxide is a "potassium channel blocker," using a sophistic laboratory technique called "patch clamp" to measure signal conduction. Findings confirmed that the compound prevents the exposed channels from leaking electrical current and enhances nerve conduction in segments of the damaged spinal cord. The compound could make it possible to sidestep spinal cord damage by enabling axons to transmit signals as though they were still sheathed in myelin.

As per the claim by the researchers, the new compound is about 10 times more potent than 4-aminopyridine, meaning lower doses can be used to reduce the likelihood of serious side effects. Because myelin also is damaged in multiple sclerosis, the same drug might be used to restore nerve function in people stricken with the disease. Hope in the days to come patients suffering from Multiple sclerosis and spinal cord injuries will breathe a sigh of relief...

Ref : J Neurophysiol (November 18, 2009). doi:10.1152/jn.00154.2009.

Sunday, November 22, 2009

Antioxidant in the vegetables for treating Cystic Fibrosis.....

I did mention in my earlier blogs, about the importance of eating broccoli and how it helps to prevent cancer and the authors claimed that the key ingredient that is responsible for this activity (claimed by the authors) is sulforaphane.

Now researchers from the University of Pennsylvania, have found an interesting fact that the antioxidant thiocyanate normally existing in the body protects lung cells from injuries caused by accumulations of hydrogen peroxide and hypochlorite, the active ingredient in household bleach. These potentially harmful chemicals are made by the body as a reaction to infection and injury. In addition, thiocyanate also protects cells from hypochlorite produced in reactions involving MPO, an enzyme released from germ-fighting white blood cells during inflammation.

The research team demonstrated that in three additional cell types used to extend their ideas to other inflammation-related conditions - cardiovascular disease, neurodegeneration, and diabetes - thiocyanate at blood concentrations of at least 100 micromolar (micromoles per liter) greatly reduces the toxicity of MPO in cells, including those lining blood vessels. Humans naturally derive thiocyanate from some vegetables and blood levels of thiocyanate in the general population vary from 10 to 140 micromolar.

So without an adequate dietary supply of thiocyanate (from broccoli & Cauliflower), hypochlorite produced by the body during inflammation would cause additional collateral damage to cells, thus worsening inflammatory diseases, and predisposing humans to diseases linked to MPO activity, including atherosclerosis. Thus the authors claim that delivering thiocyanate directly to the digestive and respiratory systems might be a therapy for CF disease.

Ref :
http://www.pnas.org/content/early/2009/11/11/0911412106.full.pdf+html?sid=2078aa5c-20d6-4a74-b98a-2a5ef6df93d4

Saturday, November 21, 2009

Bacterially produced antifungal on skin of amphibians may protect against lethal fungus

Bacterially produced antifungal on skin of amphibians may protect against lethal fungus

Adding one single gene to yeast dramatically improves bioethanol production from agricultural waste

Adding one single gene to yeast dramatically improves bioethanol production from agricultural waste

Picoplatin a better drug than oxaliplatin for colorectal cancer !


In one of my earlier blog, I did mention about the Cisplatin (Cisplatin doubles lung cancer survival time in mice !).

About Cis-platin & other drivatives:

Cisplatin, cisplatinum, or cis-diamminedichloroplatinum(II) is a platinum-based chemotherapy drug used to treat various types of cancers, (sarcomas, some carcinomas (small cell lung cancer, and ovarian cancer), lymphomas, and germ cell tumors. It was the first member of a class of anti-cancer drugs which now also includes carboplatin and oxaliplatin. These platinum complexes react in vivo, binding to and causing crosslinking of DNA which ultimately triggers apoptosis (programmed cell death).

Now its the turn of Picoplatin [see structure , Amminedichloro(2-methylpyridine)platinium)], Poniard Pharmaceuticals, Inc. has come up with some interesting results from its Phase 2 trial of picoplatin in patients with metastatic colorectal cancer (CRC). Picoplatin, given once every four weeks in combination with 5-fluorouracil and leucovorin in the FOLPI regimen, has comparable efficacy to oxaliplatin, given in combination with 5-fluorouracil and leucovorin in the modified FOLFOX-6 regimen, as a first-line therapy for CRC, as assessed by one-year survival rate, progression-free survival (PFS) and disease control. The company claims that, (from the updated proof-of-concept Phase 2 safety and efficacy results) picoplatin could be superior to oxaliplatin as a neuropathy-sparing alternative when used in combination as a first-line treatment for metastatic colorectal cancer.

Source : http://investor.poniard.com/ReleaseDetail.cfm?ReleaseID=424813.

Friday, November 20, 2009

Positive results from mipomersen- a new hope for FH sufferers...

About Familial hypercholesterolemia :

Familial hypercholesterolemia (also spelled familial hypercholesterolaemia) is a genetic disorder characterized by high cholesterol levels, specifically very high low-density lipoprotein (LDL, "bad cholesterol") levels, in the blood and early cardiovascular disease. Many patients have mutations in the LDLR gene that encodes the LDL receptor protein, which normally removes LDL from the circulation, or apolipoprotein B (ApoB), which is the part of LDL that binds with the receptor; mutations in other genes are rare. Patients who have one abnormal copy (are heterozygous) of the LDLR gene may have premature cardiovascular disease at the age of 30 to 40. Having two abnormal copies (being homozygous) may cause severe cardiovascular disease in childhood. Heterozygous FH is a common genetic disorder, occurring in 1:500 people in most countries; homozygous FH is much rarer, occurring in 1 in a million births.

Heterozygous (FH) is normally treated with statins, bile acid sequestrants or other hypolipidemic agents that lower cholesterol levels. New cases are generally offered genetic counseling. Homozygous FH often does not respond to medical therapy and may require other treatments, including LDL apheresis (removal of LDL in a method similar to dialysis) and occasionally liver transplantation.

Recently, Genzyme Corp. and Isis Pharmaceuticals Inc have come up with some intresting results from the drug mipomersen [mipomersen - is an antisense oligonucleotide, with phosphorothioate linkage at 5'- postion and 2'-O-methoxymethyl moety] ( phase 3). As per the claim by the companies, the study met its primary endpoint in an intent-to-treat analysis, with a 25 percent reduction in LDL-cholesterol after 26 weeks of treatment, vs. 3 percent for placebo (p<0.001)>.

The trial met all of its secondary and tertiary endpoints, suggesting that mipomersen may offer potential benefits to patients beyond LDL-C reduction. Patients treated with mipomersen experienced a 27 percent reduction in apolipoprotein B vs. 3 percent for placebo; a 21 percent reduction in total cholesterol vs. 2 percent for placebo; and a 25 percent reduction in non-HDL cholesterol vs. 3 percent for placebo (all p<0.001).>Mipomersen patients’ HDL-C levels increased 15 percent (p=0.035 vs. placebo), which combined with the LDL-C reductions observed, resulted in improved LDL/HDL ratios, a ratio considered an important measure of cardiovascular risk. Mipomersen patients’ LDL/HDL ratios decreased by 34% (p<0.001>Mipomersen a representative of Isis’ leadership in the field of RNA targeted therapeutics will bring a sigh of relief to the sufferers of FH, in the days to come.

I had an opportunity to work with ISIS (as contract R & D, Innovasynth Technologies Limited, Khopoli) and really excited to see the results..

Ref : http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-newsArticle&ID=1356364&highlight=

Thursday, November 19, 2009

Tranexamic acid for menorrhagia.....


Tranexamic acid (marketed as Cyklokapron in the U.S. and as Transamin in Asia, and Espercil in South America) is often prescribed for excessive bleeding. It is an antifibrinolytic that competitively inhibits the activation of plasminogen to plasmin, a molecule responsible for the degradation of fibrin. Fibrin is the basic framework for the formation of a blood clot in hemostasis. It has roughly 8 times the antifibrinolytic activity of an older analogue, ε-aminocaproic acid.

The U.S. Food and Drug Administration on 16th Nov., 2009 approved Lysteda tablets (tranexamic acid), the first non-hormonal product cleared to treat heavy menstrual bleeding (menorrhagia). Lysteda works by stabilizing a protein that helps blood to clot. Tranexamic acid was first approved by the FDA in 1986 as an injection, under the brand name Cyklokapron, and is used to reduce or prevent bleeding during and following tooth extraction in patients with hemophilia, a hereditary bleeding disorder caused by the lack of a blood clotting factor.

Source : http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm190551.htm

Tuesday, November 17, 2009

Capecitabine combination therapy reduces early breast cancer recurrence...

Capecitabine, is an orally-administered chemo therapeutic agent used in the treatment of metastatic breast and colorectal cancers.

Mode of action :

Capecitabine is a prodrug, that is enzymatically converted to 5-fluorouracil in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue. The activation of capecitabine follows a pathway with three enzymatic steps and two intermediary metabolites, 5'-deoxy-5-fluorocytidine (5'-DFCR) and 5'-deoxy-5-fluorouridine (5'-DFUR), to form 5-fluorouracil. Its being used (& FDA approved) in the treatment of adjuvant in colorectal cancer, metastatic colorectal cancer and Metastatic breast cancer - used in combination with docetaxel, after failure of anthracycline-based treatment. Also as monotherapy, if the patient has failed paclitaxel-based treatment, and if anthracycline-based treatment has either failed or cannot be continued for other reasons.

Recently, Finnish Breast Cancer Group and published in The Lancet Oncology shows women at intermediate to high-risk of early breast cancer recurrence who received capecitabine as part of their chemotherapy regimen had a 34% reduction in the risk of the disease returning or death, compared with those taking the chemotherapy combination regimen without capecitabin. The pre-planned three-year interim analysis of a randomised, prospective trial compared adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for the treatment of early breast cancer with the standard, non-capecitabine regimen (docetaxel, epirubicin, cyclophosphamide and fluorouracil). The analysis also found that patients taking the capecitabine-containing regimen were significantly less likely to have their cancer spread (distant metastasis) to another part of the body (a 36% reduction in risk was observed). This is the first phase III randomised trial to report efficacy of capecitabine combination therapy in the adjuvant treatment of early breast cancer.

Though capecitabine, has already been shown to be effective in patients with advanced breast cancer, but the most important conclusion the researchers have arrived is "capecitabine-containing regimen in the early stages of breast cancer may offer survival benefits for women".....

Source :http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2809%2970307-9/fulltext

Geron publish data on the stem cell research.....

In my earlier blog (Geron plans to advance clinical program for spinal cord injury), I did mention about the clinical program. Now Geron has come up with positive results. As per the claim by the company oligodendrocyte progenitor cells (OPCs) derived from human embryonic stem cells (hESCs), when transplanted into a rodent model of cervical spinal cord injury, reduced tissue damage within the lesion and improved recovery of locomotor function. These data provide preclinical proof-of-concept for the use of GRNOPC1, Geron's hESC-derived oligodendrocyte progenitor product, in patients with cervical spinal cord injuries.

Oligodendrocytes have two main functions in the spinal cord; they produce the myelin that wraps around nerve fibers to enable electrical impulse conduction and they produce other molecules (neurotrophic factors) that help to maintain nerve cells. In spinal cord injury oligodendrocytes are lost, resulting in the loss of myelin and death of nerve cells that can cause paralysis below the injury. The present study, conducted in a cervical model of spinal cord injury, adds to previous work in a thoracic model, which has demonstrated that injection of hESC-derived OPCs into the site of injury improved locomotor function with evidence of remyelination of nerve fibers.

Source : http://www.geron.com/media/pressview.aspx?id=1196


Capsaicin for Postherpetic neuralgia....

About Capsaicin :

Capsaicin,(8-methyl-N-vanillyl-6-nonenamide, (CH3)2CHCH=CH(CH2)4CONHCH2C6H3-4-(OH)-3-(OCH3)) is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact. Capsaicin and several related compounds are called capsaicinoids and are produced as a secondary metabolite by chili peppers, probably as deterrents against certain herbivores and fungi. Pure capsaicin is a hydrophobic, colorless, odorless, crystalline to waxy compound.

We know that many pain killer gels are using this and even some companies are trying to establish the anti cancer activity (prostate cancer).

Mode of action :

The burning and painful sensations associated with capsaicin result from its chemical interaction with sensory neurons. Capsaicin, as a member of the vanilloid family, binds to a receptor called the vanilloid receptor subtype 1 (VR1). The resulting depolarization of the neuron stimulates it to signal the brain. By binding to the VR1 receptor, the capsaicin molecule produces the same sensation that excessive heat or abrasive damage would cause, explaining why the spiciness of capsaicin is described as a burning sensation.

Now FDA has approved the Qutenza(TM) (capsaicin) 8% patch, the first and only product containing prescription strength capsaicin, for the management of neuropathic pain due to postherpetic neuralgia (PHN). As per the claim by the company, Qutenza works by targeting certain pain nerves in the area of skin where pain is being experienced. The Qutenza patch is applied by a physician or a healthcare professional. Clinical studies have shown that PHN pain can be reduced for up to 12 weeks following a single one-hour treatment. Up to four patches may be used and patches may be cut to conform to the size and shape of the painful area.

Source : http://ngsx.client.shareholder.com/releasedetail.cfm?ReleaseID=424559

Monday, November 16, 2009

Memantine for Huntington's disease ?


Memantine is the first in a novel class of Alzheimer's disease medications acting on the glutamatergic system by blocking NMDA glutamate receptors. Memantine is marketed under the brands Axura and Akatinol by Merz, Namenda by Forest, Ebixa and Abixa by Lundbeck and Memox by Unipharm.

Now researchers from Burnham & University of California have found that, Memantine, which is approved to treat Alzheimer's disease, successfully treated Huntington's disease in a mouse model by preserving normal synaptic electrical activity and suppressing excessive extrasynaptic electrical activity.

Huntington's disease is a hereditary condition caused by a mutated huntingtin gene that creates a misfolded, and therefore dysfunctional, protein. The new research shows that normal synaptic receptor activity makes nerve cells more resistant to the mutant proteins. However, excessive extrasynaptic activity contributed to increased nerve cell death. The research team found that low doses of Memantine reduce extrasynaptic activity without impairing protective synaptic activity.

This finding is of great importance because of the fact that chronic neurodegenerative diseases like Huntington's, Alzheimer's and Parkinson's are all related to protein misfolding and the researchers have shown for the first time that that electrical activity controls protein folding, and if one has a drug that can adjust the electrical activity to the correct levels, one can protect against misfolding and also the research verifies that appropriate electrical activity is protective. They also found that normal synaptic activity was protective. Subsequently, they treated Huntington's disease model mice with both high and low doses of Memantine and found that the low doses were protective by blocking pathological extrasynaptic activity, while high-dose Memantine encouraged disease progression because it also blocked the protective synaptic NMDA receptor activity. Its really good achievement congratulations. After having small clinical trials, larger, international clinical trials are now being planned....


Source : http://www.eurekalert.org/pub_releases/2009-11/bi-rfp111309.php.


Pentamidine for muscle-wasting-disease.....


Pentamidine (salt of isethionate) is an antimicrobial medication primarily given for prevention and treatment of Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii, also formerly known as Pneumocystis carinii pneumonia (PCP), a severe interstitial type of pneumonia often seen in patients with HIV infection. PCP is considered an 'opportunistic infection', endangering only immunodeficient patients such as those with HIV/AIDS. Pentamidine is also used as a prophylactic in patients receiving chemotherapy, as they also have a depressed immune system as a direct side-effect of the drugs used. The mortality of untreated PCP is very high. Additionally, pentamidine has good clinical activity in treating leishmaniasis, sleeping sickness caused by different strains of Trypanosoma, and yeast infections caused by the organism Candida albicans. Pentamidine is also used as a prophylactic antibiotic for children undergoing treatment for leukemia.

Apart from these diverse applications Pentamidine, has been recently found to become a new therapy for an inherited muscular wasting disease, according to researchers at the University of Oregon and the University of Rochester School of Medicine and Dentistry in New
York.

Pentamidine, when tested in genetically altered mice, counters genetic splicing defects in RNA that lead to type 1 myotonic dystrophy - one of nine types of muscular dystrophy -- also known as DM1 and Steinart's disease. Researchers found that pentamidine disrupted the complexes formed by the expanded repeats and the MBNL protein that becomes stuck to them, allowing the protein to return to its proper location in the cell. The compound also inhibited interactions of MBNL with the cytosine-uracil-guanine repeats and partially rescued two splicing errors in the mice. Though further study like testing with patients suffering from DM1 is still to be established, its a good achievement.

Source : http://uonews.uoregon.edu/archive/news-release/2009/11/possible-help-fight-against-muscle-wasting-disease

Statins as anticancer and anti diabetic agents ?

We know that statins are widely used as cholesterol lowering drugs. They act by inhibiting HMG-CoA reductase, the rate-limiting enzyme in the mevalonate pathway that leads to the synthesis of farnesyl pyrophosphate, a precursor for cholesterol synthesis and the source of lipid moieties for protein prenylation. But researchers from University of Gothenburg, have found that statins might be useful as anticancer and antidiabetic too.

Statins lower cholesterol by blocking certain enzymes involved in our metabolism. However, they have also been shown to affect other important lipids in the body, such as the lipids that help proteins to attach to the cell membrane (known as lipid modification). Because many of the proteins that are lipid-modified cause cancer, there are now hopes that it will be possible to use statins in the treatment of cancer.

Studies show that statins can have a dramatic inhibitory effect on growth and development. As the researchers managed to identify the enzyme involved, they can also explain how the effect arises at molecular level. Not least that they can prevent the growth of cancer cells caused by lipid-modified proteins, but also that they can be effective in the treatment of diabetes and neurological disorders such as Parkinson's. In one of my earlier blog, I have mentioned about the simvastin (Simvastatin prevents progression of Parkinson's Disease ?).

So in the days to come statins may be useful as anticancer, anti diabetic and even to treat Parkinsons disaese....


Source : http://www.science.gu.se/english/News/News_detail/Cholesterol-lowering_medicines_may_be_effective_against_cancer.cid898016

Sunday, November 15, 2009

A tetracycline derivative for the treatment of Spinal Muscular Atrophy .....

A chemical cousin of the common antibiotic tetracycline (PTK-SMA1) might be useful in treating spinal muscular atrophy (SMA), a currently incurable disease that is the leading genetic cause of death in infants. This is the finding of a research collaboration involving Adrian Krainer, Ph.D., of Cold Spring Harbor Laboratory (CSHL) and scientists from Paratek Pharmaceuticals and Rosalind Franklin University of Medicine and Science.

About SMA :

SMA is caused by mutations in a gene called Survival of Motor Neuron 1 (SMN1), resulting in a decrease in the levels of SMN protein in the motor neurons of the spinal cord -- the cells that control muscle activity. Without the protein, these neurons degenerate, and infants born with the mutations progressively lose the ability to move, swallow, and breathe. There are no approved therapies for the treatment of SMA.

Mode of action of PTK-SMA1 :

The new molecule boosts the levels of SMN protein in cells by fixing a mistake in a cellular processing mechanism called RNA splicing. The drug candidate targets the splicing of a gene called SMN2, which is essentially a back-up copy to the SMN1 gene that’s mutated beyond repair in SMA patients. SMN2 doesn’t compensate for the loss of SMN1, however, because it produces too little functional protein. Most of the protein that is produced is missing a single important piece, without which the protein rapidly degrades. The significance of this finding is in the fact that “PTK-SMA1 is the only small molecule known to specifically alter RNA splicing by directly and solely targeting the splicing reaction” . Other molecules that affect splicing also affect other cellular processes, thus diluting their potency, and potentially increasing the risk of side effects. PTK-SMA1 has the added advantage of being a derivative of tetracyclines, which are nontoxic and have demonstrated safety in humans...

Source : http://stm.sciencemag.org/content/1/5/5ra12.abstract.





Embryonic Stem Cell Therapy Restores Walking Ability In Rats With Neck Injuries..

The first human embryonic stem cell treatment approved by the FDA for human testing has been shown to restore limb function in rats with neck spinal cord injuries -- a finding that could expand the clinical trial to include people with cervical damage.

More....Embryonic Stem Cell Therapy Restores Walking Ability In Rats With Neck Injuries

Saturday, November 14, 2009

Simvastatin prevents progression of Parkinson's Disease ?


About Simvastin :
Simvastatin
, (marketed under the names Zocor, Simlup, Simcard, Simvacor) is a hypolipidemic drug belonging to the class of pharmaceuticals called "statins". It is used to control hypercholesterolemia and to prevent cardiovascular disease. Simvastatin is a synthetic derivate of a fermentation product of Aspergillus terreus. When I was working with Bangalore based company, the sister company was working on it and now its marketing too.

Recently researchers from the Rush University, have found an interesting fact that Simvastin, may prevent Parkinson's disease from progressing further. The authors have shown that the activity of one protein called p21Ras is increased very early in the midbrain of mice with Parkinson's pathology. Simvastatin enters into the brain and blocks the activity of the p21Ras protein and other associated toxic molecules, and goes on to protect the neurons, normalize neurotransmitter levels, and improves the motor functions in the mice with Parkinson's.

If the researchers are able to replicate these results in Parkinson's patients in the clinical setting, it would be a remarkable advance in the treatment of this devastating neurodegenerative disease. Hope some relief to the sufferers of Parkinson disease....

Ref : http://www.rush.edu/webapps/MEDREL/servlet/NewsRelease?id=1304

Mayan Calendar / 2012 Hoax Explained

Mayan Calendar / 2012 Hoax Explained...

But don't miss the movie based on this story..

Friday, November 13, 2009

Sprycel (Dasatinib) for ovarian cancer ?


Dasatinib, is a cancer drug produced by Bristol-Myers Squibb and sold under the trade name Sprycel. Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinases inhibitor approved for use in patients with chronic myelogenous leukemia (CML) after imatinib treatment and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). It is also being assessed for use in metastatic melanoma. Its named after Jagabandhu Das, who was a member of the large discovery and development team at Bristol Myers Squibb.

Recently, researchers with UCLA's Jonsson Comprehensive Cancer Center found that Sprycel, significantly inhibited the growth and invasiveness of ovarian cancer cells and also promoted their death. The drug, when paired with a chemotherapy regimen, was even more effective in fighting ovarian cancer in cell lines in which signaling of the Src family kinases, associated with the deadly disease, is activated. The researchers are excited because of the fact that "recent gene expression studies have shown that about one-third of women have ovarian cancers with activated Src pathways", so the drug could potentially help 7,000 ovarian cancer patients every year. Gottfried Konecny (lead researcher) said, it also inhibits the focal adhesion kinase and ephrin receptor, (drug is known to inhibit in many pathways) also associated with ovarian cancer. Though clinical trials are still to be established , its a remarkable achievement. More details .....


Electricity from sugarcane biomass...

Engineer Vikram Seebaluck of the University of Mauritius and energy technology Dipeeka Seeruttun of the Royal Institute of Technology, in Stockholm, Sweden, have demonstrated that an optimal blend of sugarcane agricultural residues (30%) mixed with 70% sugarcane bagasse (the fibrous residue left after sugar production) can be used to generate electricity at a cost of just 0.06 US dollars per kilowatt hour. That figure is on a par with the costs of other renewable energies, including wind power at $0.05/kWh.

Currently, sugarcane bagasse is burnt for onsite heat and electricity production at sugar factories and surplus electricity is exported to the grid. That still leaves 24 tonnes per hectare of waste in the fields. As per the claim by the researchers, the waste has a similar energy content to bagasse, which could make it technically viable to use this material together with bagasse in a more effective way for electricity production. The 30:70 mixture of waste and bagasse reduces the risk of fouling or slagging of the furnaces used to burn the material. I would say a kannada proverb "kasadinda rasa"..(meaning sweet solution from the waste)

Ref : http://www.inderscience.com/search/index.php?action=record&rec_id=29081&prevQuery=&ps=10&m=or

Wednesday, November 11, 2009

Anti-aging products from Schisandra Chinesis..



Schisandra (Magnolia Vine) is a genus of shrub commonly grown in gardens. Species include S. chinensis, S. glaucescens, S. rubriflora and S. rubrifolia. (picture right side : Schisandra Chinensis). In traditional Chinese medicine it is used as a remedy for many ailments: to resist infections, increase skin health, and combat insomnia, coughing, and thirst.

Recently, Glissandra Skincare Inc, announced the launch of three anti-aging products. As per the claim by the company, the key ingredient is Glissandrin,™ an exclusive suite of powerful extracts from the Schisandra berry (see above picture).

In both in-vitro and in-vivo studies, the proprietary Glissandrin formulation has proven effective in improving the visible signs of skin aging. Glissandrin does not change the cells, it nourishes them with a unique combination of natural ingredients and advanced technology, thereby supporting the healthiness of the skin cells and helping to sustain their natural ability to combat the leading causes of skin aging.

Ref : http://www.glissandra.com/story.html

Researchers discover cells that protect the respiratory tract from developing an allergic response

Researchers discover cells that protect the respiratory tract from developing an allergic response

FDA approves Romidepsin for CTCL....


We knew that, Romidepsin (Istodax), is an anticancer antibiotic undergoing clinical trials as a treatment for cutaneous T-cell lymphoma, peripheral T-cell lymphoma, and a variety of other cancers.

About Romidepsin :

Romidepsin, is a natural product obtained from the bacteria Chromobacterium violaceum, and works by blocking enzymes known as histone deacetylases and inducing apoptosis in tumor cells. It is sometimes referred to as depsipeptide, after the class of molecules to which it belongs.

FDA Approval ( Nov. 6, 2009) : The U.S. Food and Drug Administration has approved Istodax (romidepsin), an injectable medication, for treatment of patients with a rare form of cancer known as Cutaneous T-cell Lymphoma (CTCL). Patients with localized CTCL on the skin are treated with topical agents or phototherapy, but chemotherapy may be used if the cancer advances. Istodax interferes with processes required for cell replication. It is intended to be used in patients when CTCL gets worse or comes back after at least one other type of chemotherapy has been used. Other drugs approved for CTCL are Zolinza (vorinostat), Ontak (denileukin difitox), and Targretin (bexarotene). More...

Tuesday, November 10, 2009

Yoga practitioners have a healthy heart

Yoga practitioners have a healthy heart

Results of Phase 3 study of fidaxomicin...


We know that Fidaxomicin (also known as lipiarmycin, lipiarmycin A3, tiacumicin B, clostomicin B1, and OPT-80) is a new narrow spectrum macrocyclic antibiotic drug and being developed by Optimer Pharmaceuticals for treatment of Clostridium difficile infection. It works by inhibiting the bacterial enzyme RNA polymerase. It is active against gram positive bacteria especially clostridia.

Recently, Optimer Pharmaceuticals, Inc. (2. Nov, 2009) announced the presentation of new data from fidaxomicin's North American phase 3 study at the 47th Annual Meeting of the Infectious Diseases Society of America (IDSA) in Philadelphia, PA. The results are really encouraging and as per the claim by the company fidaxomicin is associated with faster resolution of diarrhea. In patients with more pronounced diarrhea (ie. not resolving in the first 24 hours of therapy), fidaxomicin was associated with a faster time to resolution of diarrhea than vancomycin (79 hrs vs. 105 hrs). The company claims that the faster time to resolution of diarrhea and improved outcomes for patients requiring concomitant antibiotics are important factors for physicians to consider when selecting a treatment for CDI more interesting factor is the significantly lower recurrence rate and higher global cure rate..

Ref : http://www.optimerpharma.com/news.asp?news_story=100&page_num=

Clinical Trial Confirms Single-Agent Efficacy of Rexin-G in Metastatic Pancreas Cancer...

Epeius Biotechnologies, confirms the first real breakthrough for pancreatic cancer seen in years; publishes a landmark report of tumor-targeted Rexin-G as stand-alone therapy in chemotherapy-resistant pancreatic cancer.

By meeting all primary and secondary study endpoints of safety and efficacy, Rexin-G has succeeded in an area of clinical oncology where many promising biologics have simply failed to deliver. By achieving both progression-free survival and overall survival benefits in pancreas cancer, while avoiding untoward systemic or dose-limiting toxicities, Rexin-G has raised the bar for the entire biopharmaceutical industry, as it inaugurates the emerging field of precision-targeted genetic medicine. The outstanding results of this advanced U.S. clinical trial confirm the results of previous preclinical and clinical studies conducted in the Philippines (where Rexin-G is approved for all solid tumors), and demonstrate beyond contestation that Rexin-G, at these effective dose levels, exhibits profound anti-tumor activity when administered as a single therapeutic agent in otherwise intractable Stage IV pancreatic cancer..

Interested one can see the mechanism of action ib this video.

Ref : http://www.epeiusbiotech.com/press-101409.asp

Monday, November 9, 2009

FDA advisory committee reviews 'azfibrocel-T' for treating wrinkles...

We know about the modern day innovative treatments for wrinkle reduction like laser skin resurfacing treatments, facelift surgery and dermal fillers such as Restylane and Botox. However, cell therapy may be on more option claims Fibrocell Science Inc (formerly Isolagen, Inc).

The company has focused on developing regenerative fibroblast cells for aesthetic, medical and scientific application. As per the claim by the company, the fibroblasts are extracted, multiplied and then re-injected into the skin as a personalized treatment, allowing for the formation of new cells and stronger connective tissue fibers. Over time, this results in a significant reduction of wrinkles and fine lines, and creates a healthier, more rejuvenated appearance. Recently (12th Oct, 2009), FDA has reviewed "azfibrocel-T, an autologous cell therapy" and the company is expecting to get green signal by January 4, 2010....

Ref : http://www.fibrocellscience.com/10_09_09.htm

Positive results from Phase 3 trial of wieght reducing drug Lorcaserin...


We knew that Lorcaserin, is a serotonergic weight-loss drug developed by Arena Pharmaceuticals. It is currently undergoing the final phase of clinical trials in preparation for submission for FDA approval.

Lorcaserin is a selective 5-HT2C receptor agonist and in vitro testing of the drug showed reasonable selectivity for 5-HT2C over other related targets 5-HT2C receptors are located almost exclusively in the brain, and can be found in the choroid plexus, cortex, hippocampus, cerebellum, amygdala, thalamus, and hypothalamus.

Mode of action : Arena believes that the activation of 5-HT2C receptors in the hypothalamus promotes weight loss through appetite suppression, and this is supported by animal studies, but it is unclear whether the dose range used in human trials will be sufficient to demonstrate the same level of weight loss. While it is generally thought that 5-HT2C receptors help to regulate appetite as well as mood, motor behavior, and endocrine secretion, the exact mechanism of appetite regulation is not yet known.

Arena reported positive, highly significant top-line results in September 2009. Arena will also present new data analyses from lorcaserin's successful Phase 3 pivotal program in oral and poster sessions. In an independent clinical symposium, expert academic scientists and physicians will spotlight the 5HT-2C mechanism for weight management. As per the claim by the company, the positive results from the Phase 3 pivotal program highlight lorcaserin's potential to provide physicians with a treatment option that combines three important attributes - efficacy, safety and tolerability. Hope in the days to come will have a drug to treat obesity too...

Ref : http://invest.arenapharm.com/releasedetail.cfm?ReleaseID=417902

Sunday, November 8, 2009

Antisense Therapeutics completes repeat-dosing toxicology studies for ATL1103

Antisense Therapeutics completes repeat-dosing toxicology studies for ATL1103

One can see the products under development...(by the same co)..

Positive Phase 2 results of Telaprevir...

I did mention about telaprevir (structure) in my earlier blog, and following other developments for hepatitis C (blogs). Now Vertex Pharmaceuticals has announced the results of Phase 2.

The results are really encouraging and as per the claim by the company "more than 80 percent of hepatitis C patients in each arm of the Phase 2 Study C208 achieved a sustained viral response (SVR) with a telaprevir-based regimen according to results of an intent-to-treat (ITT) analysis".

Across the four arms, SVR rates were 82 and 83 percent in patients treated with the every 12 hour telaprevir-based regimen (PEGINTRON and PEGASYS, respectively) and 81 and 85 percent in patients treated with the every 8 hour regimen (PEGINTRON and PEGASYS, respectively). For the majority of patients, these SVR rates were obtained with a 24-week telaprevir-based regimen.

Ref : http://investors.vrtx.com/releasedetail.cfm?ReleaseID=420611

DNA barcoding- a new window into the relations between hunter and prey in the wild ....

The scientific ability to quickly and accurately identify species through DNA "barcoding" is being embraced and applied by a growing legion of global authorities - from medical and agricultural researchers to police and customs authorities to palaeontologists and others.

More.......Third International Barcode of Life conference ......

Saturday, November 7, 2009

Methacetin breath test predicts long-term survival in patients with chronic viral hepatitis

Methacetin breath test predicts long-term survival in patients with chronic viral hepatitis

Automated Micro-injector a new tool for drug development and genetic engineering...

We had automatic synthesizers (to synthesize simultaneously many chemical intermediates, e.g., Symphony Multiplex peptide Synthesizer etc.), now its the turn of micro injector that has the potential to allow rapid development of a new generation of drugs and genetic engineering organisms, and to better control in-vitro fertilization thanx to Ravi Selvaganapathy (Asst. Prof. of Mech.Eng at McMaster Univ).

Researchers have fabricated a palm-sized, automated, micro-injector that can insert proteins, DNA and other biomolecules into individual cells at volumes exponentially higher than current procedures, and at a fraction of the cost. This will allow scientists to vastly increase preclinical trials for drug development and genetic engineering, and provide greater control of the process. As per the claim by the lead researcher Ravi, "this device is to drug discovery what the assembly line was to the automobile or the silicon chip to information technology,” Congrats for this remarkable achievement details...

Friday, November 6, 2009

Bortezomib for bone cancer in children & teens..


We knew that Bortezomib marketed as Velcade by Millennium Pharmaceuticals is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma (2008). In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease.

Recently researchers from University of Rochester have found more interesting fact that "bortezomib is effective against bone cancer in human cancer cell studies and in mice". In the current study, researchers sought to use Bortezomib (Velcade) against osteosarcoma, an aggressive cancer that starts in bone, spreads quickly and responds poorly to current chemotherapies. The drug, a proteasome inhibitor.

The researchers are excited because of the fact that "a drug already proven safe and effective in treating the most common cancers of the blood may be equally effective in suppressing bone cancer". Bortezomib caused osteosarcoma cells to self destruct, and prevented their spread. claims the researchers. While further studies are needed, these findings suggest that this drug may represent a new treatment option for a devastating disease and an effective complement to current chemotherapies. Congrats for this achievement.

More : http://www.urmc.rochester.edu/news/story/index.cfm?id=2676



Thursday, November 5, 2009

Lovastatin-synthesizing enzyme successfully reconstituted...


Lovastatin is a member of the drug class of statins, used for lowering cholesterol (hypolipidemic agent) in those with hypercholesterolemia and so preventing cardiovascular disease. Lovastatin is a naturally occurring drug found in food such as oyster mushrooms and red yeast rice. When I was working with a Banglore based company (Biocon), they did try this compound and I think the company is marketing this drug now. As for as my knowledge goes there were two ways to synthesise 'biosynthesis using Dield-Alder catalyzed cyclization' & 'biosyntheis using broadly specific acyltransferase'

Dield-Alder catalysed cyclisation : In vitro formation of a triketide lactone using a genetically-modified protein derived from 6-deoxyerythronolide B synthase has been demonstrated. The stereochemistry of the molecule supports the intriguing idea that an enzyme-catalyzed Diels-Alder reaction may occur during assembly of the polyketide chain. It thus appears that biological Diels-Alder reactions may be triggered by generation of reactive triene systems on an enzyme surface.

Biosynthesis using broadly specific acyltransferase : It has been found that a dedicated acyltransferase, LovD, is encoded in the lovastatin biosynthetic pathway. LovD has a broad substrate specificity towards the acyl carrier, the acyl substrate and the decalin acyl acceptor. It efficiently catalyzes the acyl transfer from coenzyme A thoesters or N-acetylcysteamine (SNAC) thioesters to monacolin J. The biosynthesis of lovastatin is coordinated by two iterative type I polyketide syntheses and numerous accessory enzymes. Nonketide, the intermediate biosynthetic precursor of lovastatin, is assembled by the upstream megasynthase LovB (also known as lovastatin nonaketide synthase), enoylreductase LovC, and CYP450 oxygenases.

Recently more interesting out come from a group of UCLA researchers is that, for the first time thy have successfully reconstituted in the laboratory the enzyme responsible for producing the blockbuster cholesterol-lowering drug lovastatin. As per the claim by the researchers, the lovastatin-synthesizing enzyme is one of the most interesting but least understood of the polyketide synthases, which are found in filamentous fungi and which play a crucial role in the synthesis of "small molecule natural products" — pharmacologically or biologically potent compounds produced by living organisms, many of which are the active ingredients in pharmaceuticals.

This finding is of great significance because commonly used antibiotics, such as tetracycline, are produced by polyketide synthases. Polyketides represent a class of 7,000 known structures, of which more than 20 are commercial drugs, including the immunosuppressant rapamycin, the antibiotic erythromycin and the anticancer drug doxorubicin. In their study studied the enzyme that makes a small-molecule precursor to lovastatin. The real difference about this enzyme, is its extraoridnarily large size in comparison to all other enzymes so for studied. As per the claim by the lead researcher Dr. Yi Tang, "It's one of the largest enzymes ever to be reconstituted in a test tube. It is 10 times the size of most enzymes people study & the enzyme has seven active sites and catalyzes more than 40 different reactions that eventually result in an important precursor to lovastatin. Hope with this remarkable achievement, one can prepare many natural products in the lab in the days to come.

Ref : http://www.newsroom.ucla.edu/portal/ucla/ucla-engineering-researchers-have-111812.aspx

Report on the future of RNAi-based therapeutics & diagnostics

The market for RNAi-based therapeutics is forecast to grow from 2013 onwards, as the first products enter the marketplace, to generate sales in excess of US$2.9 billion by 2020. The first siRNA based therapeutics will capitalize on the demand to treat viral infections and ocular conditions and in the longer term companies will be able to target niche areas of high unmet clinical need such as cancer, cardiovascular disease, metabolic disorders, inflammatory and neurological conditions.


More.....Report on the future of RNAi-based therapeutics & diagnostics

Wednesday, November 4, 2009

Positive results from phase 3 clinical trials of Linoclotide ....


Ironwood Pharmaceuticals, Inc. and Forest Laboratories, Inc. recently announced positive top‐line results from two Phase 3 clinical trials assessing the safety and efficacy of once‐daily dosing of the investigational drug linaclotide in patients with chronic constipation (CC). Analyses of the data indicate that in both multicenter, randomized, double‐blind, placebo‐controlled trials, statistical significance was achieved for the primary endpoint of 12‐week complete spontaneous bowel movement (CSBM) overall responder at the two doses studied in each trial (133 mcg/day: p‐values≤0.0012 and 266 mcg/day: p‐values<0.0001). In both trials, statistical significance (p<0.01) was achieved for all prespecified secondary endpoints, which included measures of bloating, abdominal discomfort, and average weekly CSBMs.

About Linaclotide :

Linaclotide (see the structure) is an orally delivered peptide that acts locally in the gut with no detectable systemic exposure at therapeutic doses and is intended for once‐daily administration. Linaclotide can be synthesized by solid-phase technology using Fmoc protections. Amino acids are coupled using DCC/HOBT and Fmoc groups are removed by means piperidne .Cysteinethiol groups are protected with trityl and cleavage of the peptide from the resin is done by TFA.

Mode of action :

Linoclotide acts agonist of guanylate cyclase type‐C (GC‐C), a receptor found on the lining of the intestine. Activation of GC‐C leads to increases in intracellular and extracellular cGMP. In preclinical models, extracellular cGMP inhibited afferent nerve firing and positively affected markers of abdominal pain, while intracellular cGMP led to activation of anion channels which stimulated anion and fluid secretion into the intestine, leading to accelerated intestinal transit. Linaclotide is a first‐in‐class compound in Phase 3 clinical development for the treatment of IBS‐C and CC.

Ref : http://www.ironwoodpharma.com/newsPDF/Linaclotide.Ph3.CC.results.11.02.09.pdf

Monday, November 2, 2009

FDA authorizes emergency use of IV antiviral "Peramivir"...

As for as my knowledge goes Peramvir, is an experimental antiviral drug, and being developed by BioCryst Pharmaceuticals for the treatment of influenza. Peramivir is a neuraminidase inhibitor, acting as a transition-state analogue inhibitor of influenza neuraminidase and thereby preventing new viruses from emerging from infected cells.

The development of peramivir is supported by the US Department of Health and Human Services as part of the US government's effort to prepare against the threat of an influenza pandemic.

The drug has had a long history. An oral formulation was abandoned by Johnson and Johnson due to poor bioavailability. BioCryst Pharmaceuticals is now developing a injectable version, in partnership with Green Cross Pharmaceuticals in South Korea and with Shionogi Pharmaceuticals in Japan. The drug is in Phase II studies

More interesting recent news (Oct. 23, 2009) about this drug is that, FDA has announced the issuing of an emergency use authorization (EUA) for the investigational antiviral drug peramivir intravenous (IV) in certain adult and pediatric patients with confirmed or suspected 2009 H1N1 influenza infection who are admitted to a hospital.

Specifically, IV peramivir is authorized only for hospitalized adult and pediatric patients for whom therapy with an IV drug is clinically appropriate based on one or more of the following reasons:
  1. the patient is not responding to either oral or inhaled antiviral therapy, or
  2. when drug delivery by a route other than an intravenous route -- e.g., enteral (absorbed by the intestines) or inhaled -- is not expected to be dependable or feasible;
  3. for adults only, when the clinician judges IV therapy is appropriate due to other circumstances.....
more..

Sunday, November 1, 2009

Steroid-induced osteoporosis can now be treated with Teriparatide

Steroid-induced osteoporosis can now be treated with Teriparatide

Geron plans to advance clinical program for spinal cord injury

In my earlier blog (Euphoria over Stem Cell Therapy.....) did mentioned that, there are many companies which falsely claimed that they have got technology (stem cell treatment) to treat spinal cord injury. But an established company like Geron, has plan to advance clinical development of its human embryonic stem cell (hESC)-based product, GRNOPC1, for the treatment of spinal cord injury. The plan is expected to enable Geron to re-initiate the Phase I clinical trial of GRNOPC1 in patients with complete thoracic spinal cord injury and to support future expansion of the trial to patients with cervical injuries.


I read earlier about the preclinical studies of GRNOPC1 and the company claimed that it is developing GRNOPC1 for spinal cord injury, but is also exploring application for other neurological diseases, including multiple sclerosis, stroke and Alzheimer disease really interesting to see the results.

As I had an opportunity to talk and work (contract research) with Geron [known for its first-in-class biopharmaceuticals (especially "antisense drugs" from oligonucleotides) for the treatment of cancer and chronic degenerative diseases] company, I know its credentials and am really excited to see some interesting out come from their advance clinical program. All the best....

Ref : http://www.geron.com/media/pressview.aspx?id=1195

Botox for Chronic Regional Pain Syndrome (CRPS). ...


We know that Botulinum toxin is a medication and a neurotoxic protein produced by the bacterium Clostridium botulinum, and is held to be the most toxic substance known to mankind with an LD50 of roughly 0.005-0.05 µg/kg. Despite its greatest known toxic effect, it is also used in very small doses to treat muscle spasms. The acceptance of BTX-A use for the treatment of spasticity and muscle pain disorders is growing, with approvals pending in many European countries and studies on headaches (including migraine), prostatic symptoms, asthma, obesity and many other possible indications are ongoing.

But some interesting findings of the same drug has been presented at the American Society of Plastic Surgeons (ASPS) Plastic Surgery 2009 conference, Oct. 23-27, in Seattle, i.e., botox can be used as a pain medication to fight Chronic Regional Pain Syndrome (CRPS).

The study found injecting Botox into the area affected by pain provides significant pain control. Eight patients suffering from severe pain received an average of nine injections , one every four weeks. All of patients reported a significant improvement (31.25 percent) in their daily pain control that was maintained for up to 17 months. Though the drug has been used to treat many problems like cervical dystonia (CD), strabismus, blepharospasm, primary axillary hyperhidrosis, glabellar lines (wrinkle fighter). this finding is more significant....

Ref : http://www.plasticsurgery.org/Documents/Media/ps2009/19-Botox-Chronic-Pain.pdf