New class of highly potent antimalarial compounds discovered

In a recent work published online today in the journal PNAS, researchers at the Instituto de Medicina Molecular (IMM), in Lisbon, Portugal, have discovered a new class of highly potent antimalarial compounds. These compounds, referred to as Torins, were originally developed by researchers in the Boston, MA to inhibit a key human protein involved in cell growth, mTOR, and have been shown to be effective anticancer agents in rodent models. In research perdormed by Dr. Kirsten Hanson in the laboratory of Dr. Maria Mota, the IMM team and their collaborators have discovered that Torins are extremely effective multistage antimalarials; Torins appear to have a novel activity against the Plasmodium parasites themselves, distinct from both currently used malaria therapeutics and from their ability to target human mTOR.

Torins are capable of killing the cultured blood stages of the human parasite, Plasmodium falciparum, the species which causes most malaria deaths and severe disease, and are equally potent against the liver stages of a model rodent parasite. A single dose of the compound Torin2 delivered at the beginning of the P. berghei liver stage is sufficient to eliminate infection in mice before any Plasmodium parasites reach the blood. "Given the alarming trend of resistance to our current antimalarial therapies, this is really an exciting finding," says Dr. Mota, the senior author of the study, "and we are already working to develop Torin molecules suitable for clinical trials of antimalarial activity in humans."

 Ref : http://www.pnas.org/content/early/2013/07/03/1306097110.full.pdf+html

New class of highly potent antimalarial compounds discovered

Scientists show how DHA resolves inflammation

In continuation of my update on DHA.

Chronic inflammation is a major factor in a wide range of problems from arthritis to cardiovascular disease, and DHA (struct above, found in fish oil) is known to temper this problem. A new research report appearing in the July 2013 issue of The FASEB Journal, helps explain why DHA is important in reducing inflammation, and provides an important lead to finding new drugs that will help bring people back to optimal health. Specifically, researchers found that macrophages (a type of white blood cell) use DHA to produce "maresins," (struct below) which serve as the "switch" that turns inflammation off and switches on resolution...

Scientists show how DHA resolves inflammation

The ribosome: New target for antiprion medicines

New research results from Uppsala University, Sweden, show that the key to treating neurodegenerative prion diseases such as mad cow disease and Creutzfeldt-Jakob disease may lie in the ribosome, the protein synthesis machinery of the cell. The results were recently published in the Journal of Biological Chemistry.

"We have now shown that the protein folding activity of the ribosome (PFAR) is most likely involved in prion propagation and thus, can be a specific target for antiprion medicines. If we understand the mechanism fully, we will be able to find ways to stop that too.," says Suparna Sanyal, senior lecturer at the Department of Cell and Molecular Biology, Uppsala University .

The ribosome is the protein synthesis machinery of the cell. The mechanism of protein synthesis by the ribosome is well characterized, while PFAR is a rather recent discovery. PFAR is a ribosomal RNA dependent function of the large subunit of the ribosome irrespective of its source. The PFAR center closely overlaps the peptidyl transferase center although the nucleobases responsible for these two functions are not all common.

"Our results show that two prion inhibitors 6-aminophenanthridine (left struct) and guanabenz acetate (right struct) implement antiprion activity by binding to ribosomal RNA and inhibiting PFAR. Thus, the ribosome and more specifically PFAR is the new target for antiprion medicines. Furthermore, we have developed an in vitro PFAR assay, which can be used as a platform for screening prion inhibitors in a high-throughput fashion. This assay is much more time and cost-effective than standard prion assays," says Suparna Sanyal....

 The ribosome: New target for antiprion medicines

 

Salsalate lowers blood glucose in type 2 diabetes, study suggests

In continuation of my update on Salsate

Joslin scientists report that salsalate, a drug used to treat arthritis, lowers blood glucose and improves glycemic control in type 2 diabetes. These findings, which were published today by the Annals of Internal Medicine, provide additional evidence that salsalate may be an effective drug to treat type 2 diabetes.

Ref : http://annals.org/article.aspx?articleid=1700640

Salsalate lowers blood glucose in type 2 diabetes, study suggests

Scientists identify promising antiviral compounds

Based on studies of the atomic-level structure of an enzyme that's essential for the maturation of adenovirus and how that enzyme becomes active  conducted at Brookhaven's National Synchrotron Light Source (NSLS) -- we used computational modeling to search for compounds that might interfere with this enzyme and tested the best candidates in the lab."

Out of 140,000 compounds in a national database, the scientists identified two they expect to be able to turn into antiviral agents to combat adenovirus.

This research is a great example of the potential for rational drug design…based on studies of the atomic-level structure of an enzyme…conducted at Brookhaven's National Synchrotron Light Source.

The need for such antiviral compounds stems from the diversity of human adenoviruses and their ubiquitous effects, Mangel said. Adenoviruses cause many types of respiratory diseases (including outbreaks among military recruits), childhood pneumonias, and eye infections -- and may even play a role in obesity. They are particularly dangerous for individuals with impaired immunity, such as transplant recipients and patients with AIDS.

With more than 50 varieties causing this range of diseases, it's unlikely scientists will develop a universally effective vaccine to prevent all strains of adenovirus before infection, Mangel said. But one thing all adenovirus strains share is a common mechanism of making new virus particles once an infection takes root. Targeting that mechanism with antiviral drugs -- the approach taken by the Brookhaven team -- may be a viable way to battle all adenovirus strains.

Mangel worked with fellow Brookhaven scientists William McGrath and Vito Graziano, along with Kathy Zabrocka, a student from Stanford University who was conducting an undergraduate internship in his lab. The research built on work Mangel's lab initiated years earlier to decipher the atomic-level structure of the adenovirus proteinase, an enzyme conserved throughout all strains of the virus that cleaves proteins during the assembly of new virus particles.

"Once those proteins are cleaved, the newly synthesized virus particle is infectious," Mangel explained. "If those proteins are not cleaved, then the infection is aborted. Thus, inhibitors of the adenovirus proteinase should be effective antiviral agents against all strains of adenovirus," he said.

Over several years, Mangel's group found that the activity of the enzyme was highly regulated by two cofactors, a small piece of another adenovirus protein and the viral DNA. Structures of the enzyme alone and in the presence of its cofactors, determined by x-ray crystallography at the NSLS, revealed key regions that could serve as potential targets for blocking the enzyme's activation or protein-cleaving ability.

"All that remained was to find compounds that bind to these targets to prevent the enzyme from functioning," Mangel said.

To find these compounds, the scientists used a technique called DOCKing, which entails computationally probing a region of the protein structure against databases of small molecules to determine which might bind most strongly. Out of a database of 140,000 potential compounds, the scientists identified 30 molecules predicted to fit best and ordered samples to test for inhibitor activity.

Two of the molecules (NSC-36806-left struct;  and NSC37249 right struct) that DOCKing identified turned out to be excellent inhibitors of the adenovirus proteinase. At the concentrations that inhibited the adenovirus proteinase, these same compounds did not inhibit other, similar enzymes. Thus, the compounds appear to be specific inhibitors of the adenovirus enzyme.

Ref : http://www.sciencedirect.com/science/article/pii/S0014579313003876  

The molecules identified are still too large to be delivered as drugs. So the scientists are working to pare down the size in the design of a second-generation compound based upon the binding portions of the two inhibitors. This new molecule is expected to readily enter adenovirus-infected cells and bind even more tightly to the adenovirus proteinase.

"This work should pave the way for the development of effective drugs against all types of adenovirus infections," Mangel said...

Scientists identify promising antiviral compounds

Abiraterone: Hint of considerable added benefit for patients with metastatic prostate cancer

In continuation of  my update on Abiraterone

Abiraterone acetate (abiraterone for short, trade name: Zytiga) has been approved in Germany since December 2012 for men with metastatic prostate cancer that is not responsive to hormone blockade, who only have mild symptoms or so far none at all, and in whom chemotherapy is not yet indicated. In an early benefit assessment pursuant to the "Act on the Reform of the Market for Medicinal Products" (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether abiraterone offers an added benefit compared with the present standard therapy....

Abiraterone: Hint of considerable added benefit for patients with metastatic prostate cancer

Curcumin may protect premature infants' lungs

In continuation of my update on the usefulness of Curcumin updates

Turmeric, a key ingredient in spicy curry dishes, has long been known to have medicinal values. Now new research finds a substance in turmeric, curcumin, may provide lasting protection against potentially deadly lung damage in premature infants...

A study, published online by the American Journal of Physiology, Lung Cellular and Molecular Physiology, found curcumin provided protection against bronchopulmonary dysplasia (BDP), a condition characterized by scarring and inflammation, and against hyperoxia, in which too much oxygen enters the body through the lungs, for up to 21 days after birth. A previous LA BioMed study found curcumin provided protection for up to seven days after birth.

"This is the first study to find long-term benefits of using curcumin to protect lung function in premature infants," said Virender K. Rehan, MD, the LA BioMed lead researcher who authored the study. "Curcumin is known to have potent antioxidant, anti-inflammatory and anti-microbial properties, making it a promising therapy for premature infants who require oxygen therapy after birth."

BDP is now the most common chronic lung disease of infancy in the U.S. With more premature babies surviving because of improvements in neonatal care, the cases of BPD have increased. A 2010 study found 67.3% of babies born at 22-25 weeks of gestation developed BPD, compared to 36.6% of infants born at 26-30 weeks of gestation.

Ref : http://ajplung.physiology.org/content/early/2013/06/24/ajplung.00082.2013

Curcumin may protect premature infants' lungs

Novel chemistry for new class of antibiotic

 The potential new antibiotic targets a bacterial enzyme critical to metabolic processes. The compound is a protein inhibitor which binds to the enzyme (called biotin protein ligase), stopping its action and interrupting the life cycle of the bacteria.

"Existing antibiotics target the bacterial cell membranes but this potential new antibiotic operates in a completel"

 

Ref : http://pubs.rsc.org/en/content/articlelanding/2013/sc/c3sc51127h

A ‘leaky mutant’ (SaBPL-R122G) of Staphylococcus aureus biotin protein ligase (SaBPL) is used to enhance the turnover rate for the reaction of biotin alkyne with an azide to give a triazole. This allows the enzyme to select the optimum triazole-based inhibitor using a library of such azides in a single experiment with greatly improved efficiency and sensitivity of detection, difficulties that can restrict the general utility of a multi-component in situ click approach to ligand optimisation...

Novel chemistry for new class of antibiotic

Chemistry riddle solved : The 2-norbornyl cation !

With support from Prof. Paul von Rague Schleyer from the University of Georgia, USA, a team of researchers including Prof. Dr. Ingo Krossing, Dr. Daniel Himmel, and Franziska Scholz from the Institute of Inorganic and Analytical Chemistry of the University of Freiburg and Prof. Dr. Karsten Meyer from the University of Erlangen has succeeded in capturing the 2-norbornyl cation as a crystal and determining beyond doubt the structure of this unusual and instable carbon compound. The 2-norbornyl cation is a non-classical carbocation, a molecule with a positively charged carbon atom that enters into five instead of three bonds with other atoms. Their article in the journal Science has ended a 50-year-old controversy among chemists.

Chemistry riddle solved

Smart anticancer 'nanofiber mesh'

A MANA research team has developed a new nanofiber mesh which is capable of simultaneously realizing thermotherapy (hyperthermia) and chemotherapy (treatment with anticancer drugs) of tumors. They succeeded in efficiently inducing natural death (apoptosis) of epithelial cancer cells.

Ref : http://onlinelibrary.wiley.com/doi/10.1002/adfm.201300746/abstract;jsessionid=A14E178EC5E6FC5D367A7C71FF0D30BC.d02t01



Smart anticancer 'nanofiber mesh'

Array BioPharma achieves milestone for initiation of MEK162 Phase 3 trial in patients with LGSOC

We know that, MEK162, is an oral, highly selective MEK inhibitor. In preclinical studies, MEK162 showed significant antitumor activities in cell lines and animal models. MEK162 is now being investigated in Phase I trials in advanced solid tumors. Recent research confirms that the MEK pathway acts as a central axis in the proliferation of different tumors including melanoma, non-small cell lung, head/neck and pancreatic cancers.  And MEK inhibition, either alone or in combination with other agents, is an important therapeutic strategy in treating cancer.  ARRY-162 is a novel, orally active, potent, selective, non-ATP-competitive inhibitor of MEK 1 / 2 that has the potential to treat a range of malignant diseases.

Array BioPharma achieves milestone for initiation of MEK162 Phase 3 trial in patients with LGSOC

First clinical study for development of SGX203 to treat pediatric Crohn's disease

A clinical stage biopharmaceutical company focused on developing products to treat inflammatory diseases and biodefense countermeasures where there remains an unmet medical need, announced today that it has enrolled and treated all patients in the Phase 1 Study BDP-PCD-01; the first clinical study for development of SGX203 (oral beclomethasone 17,21-dipropionate or oral BDP) for the treatment of pediatric Crohn's disease.  The SGX203 development program has previously received Fast Track and Orphan Drug designations from the US Food and Drug Administration (FDA) for oral BDP as a treatment for pediatric Crohn's disease......

First clinical study for development of SGX203 to treat pediatric Crohn's disease

Research finds fish oil DHA can reduce inflammation

In continuation of my update on fish oil benefits

A new research report appearing in the July 2013 issue of The FASEB Journal, helps explain why DHA is important in reducing inflammation, and provides an important lead to finding new drugs that will help bring people back to optimal health. Specifically, researchers found that macrophages (a type of white blood cell) use DHA to produce "maresins," which serve as the "switch" that turns inflammation off and switches on resolution.

 

"We hope that the results from this study will enable investigators to test the relevance of the maresin pathway in human disease," said Charles N. Serhan, Ph.D., a researcher involved in the work from the Brigham & Women's Hospital and Harvard Medical School in Boston, Mass. "Moreover, we hope to better understand resolution biology and its potential pharmacology so that we can enhance our ability to control unwanted inflammation and improve the quality of life."

Research finds fish oil DHA can reduce inflammation

Aspirin May Fight Cancer by Slowing DNA Damage

Researchers hypothesized that NSAIDs modulate clonal evolution by reducing SGA acquisition rate. Researchers  evaluated thirteen individuals with BE. Eleven had not used NSAIDs for 6.2±3.5 (mean±standard deviation) years and then began using NSAIDs for 5.6±2.7 years, whereas two had used NSAIDs for 3.3±1.4 years and then discontinued use for 7.9±0.7 years. 161 BE biopsies, collected at 5–8 time points over 6.4–19 years, were analyzed using 1Million-SNP arrays to detect SGAs. Even in the earliest biopsies there were many SGAs (284±246 in 10/13 and 1442±560 in 3/13 individuals) and in most individuals the number of SGAs changed little over time, with both increases and decreases in SGAs detected. The estimated SGA rate was 7.8 per genome per year (95% support interval [SI], 7.1–8.6) off-NSAIDs and 0.6 (95% SI 0.3–1.5) on-NSAIDs. Twelve individuals did not progress to EA. In ten we detected 279±86 SGAs affecting 53±30 Mb of the genome per biopsy per time point and in two researchers detected 1,463±375 SGAs affecting 180±100 Mb. In one individual who progressed to EA we detected a clone having 2,291±78 SGAs affecting 588±18 Mb of the genome at three time points in the last three of 11.4 years of follow-up. NSAIDs were associated with reduced rate of acquisition of SGAs in eleven of thirteen individuals. Barrett's cells maintained relative equilibrium level of SGAs over time with occasional punctuations by expansion of clones having massive amount of SGAs. More...

Aspirin May Fight Cancer by Slowing DNA Damage | ucsf.edu

FDA Approves Vibativ for Hospitalized Patients with Bacterial Pneumonia

We know that, Telavancin (trade name Vibativ) is a bactericidal lipoglycopeptide for use in MRSA or other Gram-positive infections. Telavancin is a semi-synthetic derivative of vancomycin. The FDA approved the drug in September 2009 for complicated skin and skin structure infections (cSSSI)...

Now U.S. Food and Drug Administration today expanded the approved use of the antibiotic Vibativ (telavancin) to treat patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by Staphylococcus aureus. Vibativ should be used for the treatment of HABP/VABP only when alternative treatments are not suitable...

FDA Approves Vibativ for Hospitalized Patients with Bacterial Pneumonia

Diabetes drug points the way to overcoming drug resistance in melanoma

Despite success with BRAFV600E inhibitors, therapeutic responses in patients with metastatic melanoma are short-lived because of the acquisition of drug resistance. Researchers  identified a mechanism of intrinsic multidrug resistance based on the survival of a tumor cell subpopulation. Treatment with various drugs, including cisplatin and vemurafenib, uniformly leads to enrichment of slow-cycling, long-term tumor-maintaining melanoma cells expressing the H3K4-demethylase JARID1B/KDM5B/PLU-1. Proteome-profiling revealed an upregulation in enzymes of mitochondrial oxidative-ATP-synthesis (oxidative phosphorylation) in this subpopulation. Inhibition of mitochondrial respiration blocked the emergence of the JARID1B^high subpopulation and sensitized melanoma cells to therapy, independent of their genotype. Our findings support a two-tiered approach combining anticancer agents that eliminate rapidly proliferating melanoma cells with inhibitors of the drug-resistant slow-cycling subpopulation.

Ref: http://www.cell.com/cancer-cell/retrieve/pii/S1535610813001967 

Diabetes drug points the way to overcoming drug resistance in melanoma

Diabetes drug shows promise in treatment of neurodegenerative disease

In continuation of my update on Pioglitazone

We know that, Pioglitazone is a prescription drug of the class thiazolidinedione (TZD) with hypoglycemic (antihyperglycemic, antidiabetic) action to treat diabetes. It is used to improve glucose control in adults over the age of 18 with type 2 diabetes. Pioglitazone is marketed as trademarks Actos in the USA, Canada, the UK and Germany, Glustin in Europe, Glizone and Pioz in India by Zydus Cadila and USV Limited, respectively and Zactos in Mexico by Takeda Pharmaceuticals....

Now Researchers in Spain have found that a drug used to control Type II diabetes can help repair the spinal cords of mice suffering from the inherited disease adrenoleukodystrophy which, untreated, leads eventually to a paralysis, a vegetative state and death. They believe that their findings may be relevant to other neurodegenerative diseases. A Phase II trial will be starting shortly. ...

More : http://brain.oxfordjournals.org/content/136/3/891.abstract?sid=08e53c88-b470-4a40-844f-4a1e57b570d9

Diabetes drug shows promise in treatment of neurodegenerative disease

Flamel Technologies Announces FDA Approval of Bloxiverz

Flamel Technologies today announced that the U.S. Food and Drug Administration (FDA) has approved the company's New Drug Application (NDA) for Bloxiverz (neostigmine (see structure below) methylsulfate), a drug used intravenously in the operating room for the reversal of the effects of non-depolarizing neuromuscular blocking agents after surgery. Flamel expects to launch Bloxiverz in July 2013 in 0.5 and 1.0 mg/mL strengths.

"We are extremely excited and pleased to receive this FDA approval for Bloxiverz, the first product from the portfolio of Éclat products acquired in March 2012," said Mike Anderson, Chief Executive Officer of Flamel.

Bloxiverz is the first FDA-approved version of neostigmine, even though other versions of neostigmine have been on the market as unapproved, grandfathered products under the Food, Drug and Cosmetic Act of 1938. Today, neostigmine is the most common agent used for the reversal of the effects of other agents used for neuromuscular blocks.

Flamel Technologies Announces FDA Approval of Bloxiverz

Small molecule could have big impact on cancer

Androgen receptors are found inside cells and have complex surfaces with multiple "docking points" where various proteins can bind to the receptor. Each docking point has a unique shape, so only a correctly shaped molecule will fit.

Androgen hormones, such as testosterone, are the primary molecules that bind to androgen receptors. Such binding sets off a chain of events that activates several different processes in the human body, including stimulating the development and maintenance of male characteristics.

Looking for a new approach to battle prostate cancer, Ahn and his colleagues keyed in on blocking a critical docking point on the androgen receptor.

"When a tumor is trying to grow, activation of this location provides what the tumor needs," Ahn said. "There are other surfaces on the androgen receptor that are free to continue working with their respective proteins and to continue functioning. We sought to block only one set of interactions that contribute to prostate cancer growth. That's why we thought our approach might lead to potent efficacy with fewer side effects."

Using computer-assisted molecular modeling, Ahn designed a helix-mimicking small molecule (see structure)

that fits precisely into a pocket on the androgen receptor that is associated with prostate cancer. Collaborating with senior study author Dr. Ganesh Raj, associate professor of urology at UT Southwestern and a specialist in treating urologic cancers, the researchers tested the compound in animal and isolated human tissue. Without exhibiting noticeable toxicity, the compound prevented the androgen receptor from recruiting its protein partners and it blocked the growth of prostate cancer cells.

According to the researchers, D2 (Methyl 4-(3-isobutoxy-4-nitrobenzamido)-3-isobutoxybenzoate, above structure)  is stable, non-toxic and efficiently taken up by prostate cancer cells. Importantly, D2 blocks androgen-induced nuclear uptake and genomic activity of the androgen receptor. Furthermore, D2 abrogates androgen-induced proliferation of prostate cancer cells in vitro with an IC₅₀ of 40 nM, and inhibits tumour growth in a mouse xenograft model. D2 also disrupts androgen receptor–coregulator interactions in ex vivo cultures of primary human prostate tumours. These findings provide evidence that targeting androgen receptor–coregulator interactions using peptidomimetics may be a viable therapeutic approach for patients with advanced prostate cancer.

"We have shown that our molecule binds very tightly, targeting the androgen receptor with very high affinity," Ahn said. "We also have confirmed that it inhibits androgen function in these cells, which is a promising finding for drug development. We showed that it does work through these mechanisms, and it is as effective in inhibiting the proliferation of prostate cancer cells as other compounds currently in clinical trials."

Read more

Ref : http://www.nature.com/ncomms/journal/v4/n5/full/ncomms2912.html

Small molecule could have big impact on cancer

FDA Approves Revlimid (lenalidomide) for the Treatment of Patients with Relapsed or Refractory Mantle Cell Lymphoma

In continuation of my update on Lenalidomide

We know that, Lenalidomide (Revlimid) is a derivative of thalidomide introduced in 2004. It was initially intended as a treatment for multiple myeloma, for which thalidomide is an accepted therapeutic treatment. Lenalidomide has also shown efficacy in the class of hematological disorders known as myelodysplastic syndromes (MDS). Lenalidomide has significantly improved overall survival in myeloma (which generally carries a poor prognosis), although toxicity remains an issue for users.

FDA Approves Revlimid (lenalidomide) for the Treatment of Patients with Relapsed or Refractory Mantle Cell Lymphoma

FDA Approves TOBI Podhaler

We know that, Tobramycin is an aminoglycoside antibiotic derived from Streptomyces tenebrarius and used to treat various types of bacteria infections, particularly Gram-negative infections. It is especially effective against species of Pseudomonas.

 

The U.S. Food and Drug Administration today approved TOBI Podhaler (tobramycin inhalation powder) for the management of cystic fibrosis patients with Pseudomonas aeruginosa, a bacterium that causes lung infections.

Press Releases: FDA approves Novarti...

Bristol-Myers Squibb Receives US FDA sNDA Approval for Use of SUSTIVA® (efavirenz) in HIV-1 Infected Pediatric Patients | BMS Newsroom

We know that, Efavirenz (EFV, brand names Sustiva, Stocrin, Efavir etc.) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and is used as part of highly active antiretroviral therapy (HAART) for the treatment of a human immunodeficiency virus (HIV) type 1.

For HIV infection that has not previously been treated, the United States Department of Health and Human Services Panel on Antiretroviral Guidelines currently recommends the use of efavirenz in combination with tenofovir/emtricitabine (Truvada) as one of the preferred NNRTI-based regimens in adults and adolescents .

Efavirenz is also used in combination with other antiretroviral agents as part of an expanded postexposure prophylaxis regimen to reduce the risk of HIV infection in people exposed to a significant risk (e.g. needlestick injuries, certain types of unprotected sex etc.).

The usual adult dose is 600 mg once a day. It is usually taken on an empty stomach at bedtime to reduce neurological and psychiatric adverse effects.

Efavirenz was combined with the popular HIV medication Truvada, which consists of tenofovir and emtricitabine, all of which are reverse transcriptase inhibitors. This combination of three medications approved by the U.S. Food and Drug Administration (FDA) in July 2006 under the brand name Atripla, provides HAART in a single tablet taken once a day. It results in a simplified drug regimen for many patients.

 

Bristol-Myers Squibb Receives US FDA sNDA Approval for Use of SUSTIVA® (efavirenz) in HIV-1 Infected Pediatric Patients | BMS Newsroom

FDA Approves Tafinlar (dabrafenib) for Advanced Melanoma

In conyinaution of my update on Dabrafenib

 

GlaxoSmithKline plc announced today that the U.S. Food and Drug Administration (FDA) has approved Tafinlar (dabrafenib). Tafinlar is indicated as a single-agent oral treatment for unresectable melanoma (melanoma that cannot be removed by surgery) or metastatic melanoma (melanoma which has spread to other parts of the body) in adult patients with BRAF V600E mutation. Tafinlar is not indicated for the treatment of patients with wild-type BRAF melanoma. The mutation must be detected by an FDA-approved test, such as the companion diagnostic assay from bioMérieux S.A., THxID™-BRAF.

FDA Approves Tafinlar (dabrafenib) for Advanced Melanoma

FDA Approves Mekinist (trametinib) for Advanced Melanoma

In continuation of my update on Trametinib

 

GlaxoSmithKline plc announced today that the U.S. Food and Drug Administration (FDA) has approved Mekinist (trametinib) as a single-agent oral treatment for unresectable or metastatic melanoma in adult patients with BRAF V600E or V600K mutations. Mekinist is not indicated for the treatment of patients who have received a prior BRAF inhibitor therapy. The mutation must be detected by an FDA-approved test, such as the companion diagnostic assay from bioMérieux S.A., THxID™-BRAF.

FDA Approves Mekinist (trametinib) for Advanced Melanoma

Cancer Fighting Foods.............

Cancer Fighting Foods:

How can food fight cancer, you ask? In many, many ways! Certain healthy foods can lower your risk for cancer by repairing damaged cells and protect sensitive skin. Incorporating more plant-based foods into your diet is a relatively small lifestyle change that can really reduce your cancer risk.

Orange Juice:

Oranges are high in folate, and recent research suggests that people with low levels of folate are more likely have mutations occur in their DNA, which can lead to mutated cancer cells.  Leafy greens, like spinach and Brussels sprouts, are also high in folate. In recent research, men who consumed their daily suggested intake of folate were able to decrease their risk for pancreatic cancer by 50-percent.

Milk:

We’ve all heard that calcium is important for healthy bones, but milk is also high in vitamin D, another nutrient that is linked to combating cancer—researchers suggest that vitamin D helps stop the growth of cancerous cells. In fact, it has been shown to significantly decrease the risk of breast cancer.

Beans:

The more you eat, the more you—well, the more you decrease your risk for cancer.  Beans, in addition to being high in protein and fiber (great for vegetarian diet), are also high in antioxidants that are key in the fight against cancer.  Antioxidants protect your cells against free radicals—free radicals, which can come from activities like smoking, cause damage to cells, leading to cancer and other complications.

Other foods that are high in antioxidants: Berries, cruciferous vegetables (think broccoli and cabbage), potatoes and nuts. A good general rule of thumb is to eat fruits and veggies that have a lot of color to them, as they usually contain the highest amount antioxidants.

Salad :

Your mom was right—you really should eat up all of your leafy greens .  Leafy greens (like spinach and kale) contain a substance called chlorophyllin, which can help fight cancer—it works by blocking toxins. People who consume more leafy greens show lower rates of stomach cancer.

And A Glass of Wine!

Grapes and wine contain resveratrol, which is another substance that slows the growth of cancerous cells. It does so by limiting growth and acts as a catalyst for apoptosis (a cancer cell death).  In addition to it’s anti-carcinogenic properties, it also helps prevent Alzheimer’s and diabetes. More importantly (ha-ha), it’s also been linked to anti-aging properties: it helps stimulate the production of SIRT1, a serum that helps slow the aging process.

So, there you have it; your first steps to prevent cancer (along with SPF and quitting smoking) are right here.  A healthier diet with more fruits and veggies will do more than lower your risk of cancer; it will change your quality of life. And, if eating healthy is not your thing, start with small changes, and build from there!

Virginia Cunningham is a freelance writer from Los Angeles whose writing covers a range of health topics, including holistic alternatives, healthy cooking and personal fitness. She not only includes these cancer-fighting foods into her diet, but she enjoys them as well!

Raptor Pharmaceutical's PROCYSBI™ Receives FDA Approval for the Treatment of Nephropathic Cystinosis

Cysteamine bitartrate,  is a cystine depleting agent which lowers the cystine content of cells in patients with cystinosis, an inherited defect of lysosomal transport. It is an aminothiol, beta-mercaptoethylamine. Cysteamine bitartrate is a highly water soluble white powder with a molecular weight of 227 and the molecular formula C₂H₇NS • C₄H₆O₆. It has the following chemical structure:

Now, U.S. Food and Drug Administration today approved Procysbi (cysteamine bitartrate) for the management of nephropathic cystinosis in children and adults. Procysbi was granted orphan product designation because it is intended to treat a rare disease or condition....

Multimedia Now Available: Raptor Pharmaceutical's PROCYSBI™ Receives FDA Approval for the Treatment of Nephropathic Cystinosis (NASDAQ:RPTP)

Arbor Pharmaceuticals Announces FDA Approval of Nymalize

We know that, Nimodipine (marketed by Bayer as Nimotop) is a dihydropyridine calcium channel blocker originally developed for the treatment of high blood pressure. It is not frequently used for this indication, but has shown good results in preventing a major complication of subarachnoid hemorrhage (a form of cerebral hemorrhage) termed vasospasm; this is now the main use of nimodipine.

Now FDA,  has approved its New Drug Application (NDA) for Nymalize (nimodipine) oral solution. Nymalize was previously granted Orphan designation which provides seven years of market exclusivity. Nymalize is the first and only nimodipine oral solution indicated for the improvement of neurological outcome in adult patients with subarachnoid hemorrhage (SAH).

Arbor Pharmaceuticals Announces FDA Approval of Nymalize

First drug to significantly improve heart failure mortality in over a decade

We know that, Coenzyme Q₁₀, also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ₁₀, CoQ, or Q₁₀ is a 1,4-benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the number of isoprenyl chemical subunits in its tail.

This oil-soluble, vitamin-like substance is present in most eukaryotic cells, primarily in the mitochondria. It is a component of the electron transport chain and participates in aerobic cellular respiration, generating energy in the form of ATP. Ninety-five percent of the human body’s energy is generated this way.  Therefore, those organs with the highest energy requirements—such as the heart, liver and kidney—have the highest CoQ₁₀ concentrations.There are three redox states of CoQ₁₀: fully oxidized (ubiquinone), semiquinone (ubisemiquinone), and fully reduced (ubiquinol). The capacity of this molecule to exist in a completely oxidized form and a completely reduced form enables it to perform its functions in the electron transport chain and as an antioxidant respectively.

Now double blind controlled trials have shown that CoQ10 improves symptoms, functional capacity and quality of life in patients with heart failure with no side effects. But until now, no trials have been statistically powered to address effects on survival.

The Q-SYMBIO study (2) randomised 420 patients with severe heart failure (New York Heart Association (NYHA) Class III or IV) to CoQ10 or placebo and followed them for 2 years. The primary endpoint was time to first major adverse cardiovascular event (MACE) which included unplanned hospitalisation due to worsening of heart failure, cardiovascular death, urgent cardiac transplantation and mechanical circulatory support. Participating centres were in Denmark, Sweden, Austria, Slovakia, Poland, Hungary, India, Malaysia and Australia.

CoQ10 halved the risk of MACE, with 29 (14%) patients in the CoQ10 group reaching the primary endpoint compared to 55 (25%) patients in the placebo group (hazard ratio=2; p=0.003). CoQ10 also halved the risk of dying from all causes, which occurred in 18 (9%) patients in the CoQ10 group compared to 36 (17%) patients in the placebo group (hazard ratio=2.1; p=0.01).

CoQ10 treated patients had significantly lower cardiovascular mortality (p=0,02) and lower occurrence of hospitalisations for heart failure (p=0.05). There were fewer adverse events in the CoQ10 group compared to the placebo group (p=0.073).

Professor Mortensen said: "CoQ10 is the first medication to improve survival in chronic heart failure since ACE inhibitors and beta blockers more than a decade ago and should be added to standard heart failure therapy."

First drug to significantly improve heart failure mortality in over a decade

Research aims for insecticide that targets malaria mosquitoes

Acetylcholinesterase helps regulate nervous system activity by stopping electrical signaling in nerve cells. If the enzyme can't do its job, the mosquito begins convulsing and dies. The research team's goal is to develop compounds perfectly matched to the acetylcholinesterase molecules in malaria-transmitting mosquitoes, he said.

"A simple analogy would be that we're trying to make a key that fits perfectly into a lock," Bloomquist said. "We want to shut down the enzyme, but only in target species."

Bloomquist and colleagues at Virginia Tech, where the project is based, are trying to perfect mosquito-specific compounds that can be manufactured on a large scale and applied to mosquito netting and surfaces where the pests might land.

It will take at least four to five years before the team has developed and tested a compound enough that it's ready to be submitted for federal approval, Bloomquist said.

As per the claims by the researchers, conventional insecticides targeting acetylcholinesterase (AChE) typically show high mammalian toxicities and because there is resistance to these compounds in many insect species, alternatives to established AChE inhibitors used for pest control are needed. Here researchers  used a fluorescence method to monitor interactions between various AChE inhibitors and the AChE peripheral anionic site, which is a novel target for new insecticides acting on this enzyme. The assay uses thioflavin-T as a probe, which binds to the peripheral anionic site of AChE and yields an increase in fluorescent signal. Three types of AChE inhibitors were studied: catalytic site inhibitors (carbamate insecticides, edrophonium, and benzylpiperidine), peripheral site inhibitors (tubocurarine, ethidium bromide, and propidium iodide), and bivalent inhibitors (donepezil, BW284C51, and a series of bis(n)-tacrines). All were screened on murine AChE to compare and contrast changes of peripheral site conformation in the TFT assay with catalytic inhibition. All the inhibitors reduced thioflavin-T fluorescence in a concentration-dependent manner with potencies (IC₅₀) ranging from 8 nM for bis(6)-tacrine to 159 μM for benzylpiperidine. Potencies in the fluorescence assay were correlated well with their potencies for enzyme inhibition (R² = 0.884). Efficacies for reducing thioflavin-T fluorescence ranged from 23–36% for catalytic site inhibitors and tubocurarine to near 100% for ethidium bromide and propidium iodide. Maximal efficacies could be reconciled with known mechanisms of interaction of the inhibitors with AChE. When extended to pest species, we anticipate these findings will assist in the discovery and development of novel, selective bivalent insecticides acting on AChE....

 Ref : http://www.sciencedirect.com/science/article/pii/S0048357513000655#f0025

Research aims for insecticide that targets malaria mosquitoes