Acid reflux drug may cause heart disease, study suggests

In human tissue and mouse models, the researchers found PPIs (proton pump inhibitors) caused the constriction of blood vessels. If taken regularly, PPIs could lead to a variety of cardiovascular problems over time, including hypertension and a weakened heart. In the paper, the scientists call for a broad, large-scale study to determine whether PPIs are dangerous.

"The surprising effect that PPIs may impair vascular health needs further investigation," said John Cooke, M.D., Ph.D., the study's principal investigator. "Our work is consistent with previous reports that PPIs may increase the risk of a second heart attack in people that have been hospitalized with an acute coronary syndrome. Patients taking PPIs may wish to speak to their doctors about switching to another drug to protect their stomachs, if they are at risk for a heart attack."

Commonly used proton pump inhibitors in the United States are lansoprazole (below left) and omeprazole (below right), 

and these drugs are purchasable over the counter as brands or generics. The FDA estimates about 1 in 14 Americans has used them. In 2009, PPIs were the third-most taken type of drug in the U.S., accounting for $13 billion in sales. PPIs are used to treat a wide range of disorders, including gastroesophageal reflux disease, or GERD, infection by the ulcer-causing Helicobacter pylori, Zollinger-Ellison syndrome, and Barrett's esophagus.

Recent studies of proton pump inhibitors use by people who've already experienced severe cardiovascular events have raised concern about the anti-reflux drugs, at least for this subgroup of patients, said Cooke, chair of the Department of Cardiovascular Sciences and director of the Center for Cardiovascular Regeneration at Houston Methodist DeBakey Heart & Vascular Center.

PPIs are initially inert. After oral consumption, they are activated by specialized cells in the stomach. Once active, the molecules suppress the movement of protons into the intestine, which reduces the amount of acid present there and in the stomach.

In mouse models and cultures of human endothelial cells, Cooke and lead author Yohannes Ghebramariam, Ph.D., found that PPIs suppressed the enzyme DDAH, dimethylarginine dimethylaminohydrolase. That caused an increase in the blood levels of ADMA (asymmetric dimethylarginine), an important chemical messenger. They found ADMA in turn suppressed the production of another chemical messenger, nitric oxide, or NO, proven by 1998 Nobel Prize winners Furchgott, Ignarro, and Murad to impact cardiovascular function. Quantitative studies in mouse models showed animals fed PPIs were more likely than controls to have tense vascular tissue.

"We found that PPIs interfere with the ability of blood vessels to relax," said Ghebremariam, a Houston Methodist molecular biologist. "PPIs have this adverse effect by reducing the ability of human blood vessels to generate nitric oxide. Nitric oxide generated by the lining of the vessel is known to relax, and to protect, arteries and veins."

The researchers found PPIs led to an approximately 25 percent increase in ADMA in mouse and tissue cultures, and reduced the ability of mouse blood vessels to relax by over 30 percent on average.

Acid reflux drug may cause heart disease, study suggests

Phase III trial shows afatinib offers clinical benefit to patients with EGFR mutation positive NSCLC

We know that, Afatinib (INN; trade name Gilotrif, previously Tomtovok and Tovok) is an approved drug against non-small cell lung carcinoma (NSCLC), developed by Boehringer Ingelheim As of July 2012, it is undergoing Phase III clinical trials for this indication and breast cancer, as well asPhase II trials for prostate and head and neck cancer, and a Phase I glioma trial. Afatinib is a first-line treatment

.

In October 2010 a Phase III trial in NSCLC patients called Lux-Lung 5 began with this drug. Fall 2010 interim results suggested the drug extendedprogression-free survival threefold compared to placebo, but did not extend overall survival. In May 2012, the Phase IIb/III trial Lux-Lung 1 came to the same conclusion.

Phase II results for breast cancer that over-expresses the protein human epidermal growth factor receptor 2 (Her2-positive breast cancer) were described as promising by the authors, with 19 of 41 patients achieving benefit from afatinib. Double-blind Phase III trials are under way to confirm or refute this finding. Her2-negative breast cancers showed limited or no response to the drug.

Mechanism of action :: Like lapatinib and neratinib, afatinib is a next generation tyrosine kinase inhibitor (TKI) that irreversibly inhibits human epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) kinases. Afatinib is not only active against EGFR mutations targeted by first generation TKIs like erlotinib or gefitinib, but also against those not sensitive to these standard therapies. Because of its additional activity against Her2, it is investigated for breast cancer as well as other EGFR and Her2 driven cancers.

Phase III trial shows afatinib offers clinical benefit to patients with EGFR mutation positive NSCLC

FDA Approves Khedezla for Major Depressive Disorder

We know that, Desvenlafaxine (brand name: Pristiq), also known as O-desmethylvenlafaxine, is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class developed and marketed by Wyeth (now part of Pfizer). Desvenlafaxine is a synthetic form of the major active metabolite of venlafaxine (sold under the brand names Effexor and Efexor). It is being targeted as the first non-hormonal based treatment for menopause. 

Now FDA Approves Khedezla for Major Depressive Disorder

FDA Approves Gilotrif for Late Stage Non-Small Cell Lung Cancer

We know that, Afatinib, trade name Gilotrif, previously Tomtovok and Tovok is an approved drug against non-small cell lung carcinoma (NSCLC), developed by Boehringer Ingelheim. As of  2012, it is undergoing Phase III clinical trials for this indication and breast cancer, as well as Phase II trials for prostate and head and neck cancer, and a Phase I glioma trial. Afatinib is a first-line treatment.

Now FDA has approved...

“Today’s approvals further illustrate how a greater understanding of the underlying molecular pathways of a disease can lead to the development of targeted treatments,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Gilotrif is the second drug approved this year for patients with untreated metastatic NSCLC whose tumors have the EGFR exon 19 deletions or exon 21 L858R substitution mutations.”

In May, the FDA approved Tarceva (erlotinib) for first-line treatment of patients with NSCLC. Tarceva’s new indication was approved concurrently with the cobas EGFR Mutation Test, a companion diagnostic to identify patients with tumors having the EGFR gene mutations.

“The approval of companion diagnostic tests and drugs are important developments in oncology, as they help us bring safe and effective treatments to patients who need them,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health...

More ....

Read more at http://www.drugs.com/newdrugs/fda-approves-gilotrif-late-stage-non-small-cell-lung-cancer-3851.html#y7iJKwGPFiGsiEPL.99 

FDA Approves Gilotrif for Late Stage Non-Small Cell Lung Cancer

Compounds outsmart solid tumors' malfunctioning machinery

In continuation of my update on Rapamycin

"Allosteric regulators are better than proteasome-affecting agents used in clinics because they do not induce classical drug resistance," Dr. Gaczynska said. "They bind to sites on the proteasome molecule used by natural regulatory proteins. They are more specific and are not restricted to proteasome inhibition but can activate the proteasome under certain conditions."

The new strategy was serendipitously found during experiments with rapamycin, a drug that in a highly publicized study by the UT Health Science Center's Barshop Institute for Longevity and Aging Studies was found to extend life span in mice.

Potential

The Molecular Pharmacology report and follow-up studies describe the unexpected and highly desired effects that rapamycin and similar compounds elicit on the proteasome. Based on these studies, it would be possible to design a new line of proteasome regulators with anti-cancer properties, Drs. Osmulski and Gaczynska said.... 

Ref : http://molpharm.aspetjournals.org/content/84/1/104

Compounds outsmart solid tumors' malfunctioning machinery

Multiple sclerosis drug shows promise for preventing heart failure

A drug already approved to treat multiple sclerosis may also hold promise for treating cardiac hypertrophy, or thickening of the cardiac muscle-a disorder that often leads to heart failure, researchers at the University of Illinois at Chicago College of Medicine report. 

Using an experimental mouse model of cardiac hypertrophy, Solaro and his team found that FTY-720 (Fingolimod, see structure) significantly reduced heart mass; lessened fibrosis, or stiffening of the heart muscle; and improved overall cardiac function in the mice that received the drug.

The researchers also showed that the drug inhibits expression of several genes involved in cardiac hypertrophy.

"We saw that FTY-720 blocked the activity of a protein we know is involved in causing heart-cell thickening," said Solaro. When that protein is blocked, he said, collagen and other proteins involved in heart-cell thickening are also down-regulated.

Collagen, a fibrous protein found between heart cells, causes the heart muscle to become stiff. Collagen is often overabundant in people with cardiac hypertrophy.

"When the heart muscle is stiff, it actually takes effort to relax the heart and allow blood to flow into the ventricles, so this is another way this disease causes the heart to work harder than it should have to," Solaro said.

"FTY-720 is a potential therapy to treat this disease and prevent heart failure for people where the disease is acquired through high blood pressure, and possibly inherited hypertrophy as well," he said.

Ref : http://circheartfailure.ahajournals.org/content/6/4/833

Multiple sclerosis drug shows promise for preventing heart failure

Study offers new hope for treatment of diffuse large B-cell lymphoma

Study offers new hope for treatment of diffuse large B-cell lymphoma

Compound Anthracimycin, discovered at sea shows potency against anthrax

Fenical's team in the Scripps Center for Marine Biotechnology and Biomedicine, working in conjunction with San Diego-based Trius Therapeutics, used an analytical technique known as spectroscopy to decipher the unusual structure of a molecule from a microscopic species known as Streptomyces. Initial testing of the compound, which they named anthracimycin, revealed its potency as a killer of anthrax, the infectious disease often feared as a biological weapon, as well as MRSA.

"The real importance of this work is the fact that anthracimycin has a new and unique chemical structure," said Fenical, who added that the finding is a basic research discovery, which could lead to testing and development, and eventually a drug. "The discovery of truly new antibiotic compounds is quite rare. This discovery adds to many previous discoveries that show that marine bacteria are genetically and chemically unique."

The discovery provides the latest evidence that the oceans, and many of its unexplored regions, represent a vast resource for new materials that could one day treat a variety of diseases and illnesses. Fenical, a distinguished professor of oceanography and pharmaceutical science, helped found the field of marine biomedicine as a researcher at Scripps. He is a pioneer in discovering and identifying these novel compounds. His research has helped bring attention to the need for continued exploration of the ocean for science and society....

More at  https://scripps.ucsd.edu/news/13060

Ref : http://onlinelibrary.wiley.com/doi/10.1002/anie.201302749/abstract

Compound discovered at sea shows potency against anthrax

Drug shows dramatic reduction in seizures in patients with tuberous sclerosis complex

In continuation of my update on Everolimus

Newest study, led by a physician-scientist at Cincinnati Children's in collaboration with a team at Texas Children's Hospital in Houston, has been accepted by the journal Annals of Neurology, and is available online.

"Everolimus treatment reduced seizure frequency and duration in the majority of TSC epilepsy patients whose seizures previously did not respond to treatment," says Darcy Krueger, MD, PhD, a pediatric neurologist at Cincinnati Children's and lead author of the study. "This improvement in seizure control was associated with a better quality of life, and side effects were limited. Work is already underway to confirm these results in a follow-up, phase III clinical study."

"This has been positively life-changing for the patients involved and is nothing short of transformative in the treatment of epilepsy associated with cellular growth disorders, such as TSC," says Angus Wilfong, MD, director of the comprehensive epilepsy program at Texas Children's Hospital and associate professor of pediatrics and neurology at Baylor College of Medicine.

The study included 20 patients who were treated with everolimus. Their median age was 8. Half of the patients were enrolled at Cincinnati Children's and half at Texas Children's Hospital in Houston.

The researchers found that everolimus reduced seizure frequency by at least 50 percent in 12 of the 20 participants. The drug also reduced seizures in 17 of the 20 TSC patients by a median rate of 73 percent. Four patients were free of seizures and seven had at least a 90 percent reduction in seizure frequency.

Overall quality of life, as reported by the participants' parents, also improved. Parents reported several positive changes, including attention, behavior, social interaction and physical restrictions.

Ref: http://onlinelibrary.wiley.com/doi/10.1002/ana.23960/abstract;jsessionid=5F1A5FDF269D16EDA880D9A0CE57B8CC.d03t03

Drug shows dramatic reduction in seizures in patients with tuberous sclerosis complex

How cranberries impact infection-causing bacteria

In continuation of my update on Cranberries

Researchers in McGill University's Department of Chemical Engineering are shedding light on the biological mechanisms by which cranberries may impart protective properties against urinary tract and other infections. Two new studies, spearheaded by Prof. Nathalie Tufenkji, add to evidence of cranberries' effects on UTI-causing bacteria. The findings also point to the potential for cranberry derivatives to be used to prevent bacterial colonization in medical devices such as catheters.

In research results published online last month in the Canadian Journal of Microbiology, Prof. Tufenkji and members of her laboratory report that cranberry powder can inhibit the ability of Proteus mirabilis, a bacterium frequently implicated in complicated UTIs, to swarm on agar plates and swim within the agar. The experiments also show that increasing concentrations of cranberry powder reduce the bacteria's production of urease, an enzyme that contributes to the virulence of infections.

These results build on previous work by the McGill lab, showing that cranberry materials hinder movement of other bacteria involved in UTIs. A genome-wide analysis of an uropathogenic E. coli revealed that expression of the gene that encodes for the bacteria's flagellar filament was decreased in the presence of cranberry PACs.

The team's findings are significant because bacterial movement is a key mechanism for the spread of infection, as infectious bacteria literally swim to disseminate in the urinary tract and to escape the host immune response.

"While the effects of cranberry in living organisms remain subject to further study, our findings highlight the role that cranberry consumption might play in the prevention of chronic infections," Tufenkji says. "More than 150 million cases of UTI are reported globally each year, and antibiotic treatment remains the standard approach for managing these infections. The current rise of bacterial resistance to antibiotics underscores the importance of developing another approach."

Ref : http://www.nrcresearchpress.com/doi/abs/10.1139/cjm-2012-0744#.UeTskY03C3E

How cranberries impact infection-causing bacteria

Phase III study: REVLIMID meets primary endpoint in patients newly diagnosed with multiple myeloma

In continuation of my update on lenalidomide

Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation (NASDAQ: CELG), recently announced that its phase III study (MM-020/IFM 07-01) of REVLIMID®(lenalidomide) in combination with dexamethasone in patients newly diagnosed withmultiple myeloma met its primary endpoint of progression-free survival (PFS). In the study, a doublet regimen of continuous oral lenalidomide in combination with low-dose dexamethasone (Rd) demonstrated a statistically significant improvement in PFS compared to patients receiving a comparator arm with a triplet regimen consisting of melphalan, prednisone and thalidomide (MPT).

Phase III study: REVLIMID meets primary endpoint in patients newly diagnosed with multiple myeloma

Scientists set out to develop safer versions of acetaminophen

Acetaminophen (ApAP) is an electron donor capable of reducing radicals generated by redox cycling of hemeproteins. It acts on the prostaglandin H synthases (cyclooxygenases; COXs) to reduce the protoporphyrin radical cation in the peroxidase site of the enzyme, thus preventing the intramolecular electron transfer that generates the Tyr385 radical required for abstraction of a hydrogen from arachidonic acid to initiate prostaglandin synthesis. Unrelated to this pharmacological action, metabolism of ApAP by CYPs yields an iminoquinone electrophile that is responsible for the hepatotoxicity, which results from high doses of the drug. Researchers synthesized novel heterocyclic phenols predicted to be electron donors. Two of these inhibited the oxygenation of arachidonic acid by PGHS-1 and myoglobin and also were shown to be more metabolically stable and exhibited less direct cytotoxicity than acetaminophen. They are leading candidates for studies to determine whether they are free of the metabolism-based hepatotoxicity produced by acetaminophen.....

Ref : http://pubs.acs.org/doi/pdf/10.1021/ml4000904

Scientists set out to develop safer versions of acetaminophen

Urocortin molecule protects cells from osteoarthritis, say researchers

We know that, Urocortin is a protein that in humans is encoded by the UCN gene. This gene is a member of the sauvagine/corticotropin-releasing factor/urotensin I family. It is structurally related to the corticotropin-releasing factor (CRF) gene and the encoded product is an endogenous ligand for CRF type 2 receptors. In the brain, it may be responsible for the effects of stress on appetite. In spite of the gene family name similarity, the product of this gene has no sequence similarity to urotensin II. Urocortin is a potent anorexigenic peptide of 40 amino acids that induces fed-like motor activity when administered centrally or peripherally in fasted animals. Urocortin belongs to the corticotropin-releasing factor (CRF) family that includes CRF, urotensin I, sauvagine, urocortin II and urocortin III. Urocortin is also a potent and long-lasting hypotensive agent and increases coronary blood flow.

Now researchers from The University of Manchester and the University of Westminster have found that the molecule, known as Urocortin, protects cells in the joints from being destroyed.

The discovery could help lead to the development of new medicines to prevent joint degradation  a condition which affects millions of people in the UK each year.

Merck Receives Complete Response Letter for Suvorexant, Merck’s Investigational Medicine for Insomnia

In continuation of my update on Suvorexant

New Drug Application Submitted to U.S. FDA for Ibrutinib in the Treatment of Two B-Cell Malignancies

We know that, Ibrutinib, also known as PCI-32765, is an experimental drug candidate for the treatment of various types of cancer. It is an orally-administered, selective and covalent inhibitor of the enzyme Bruton tyrosine kinase (Btk). Ibrutinib is currently under development by Pharmacyclics, Inc and Johnson & Johnson's Janssen.

Now Janssen Research & Development, LLC announced the submission of a New Drug Application for ibrutinib to the U.S. Food and Drug Administration (FDA) for its use in the treatment of previously treated patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and for its use in the treatment of previously treated patients with mantle cell lymphoma (MCL). The regulatory submission for ibrutinib is supported by data from two pivotal Phase 2 studies, one in relapsed/refractory CLL/SLL (PCYC-1102) and one in relapsed/refractory MCL (PCYC-1104), both of which were published in The New England Journal of Medicine online on June 19, 2013. Ibrutinib is a novel Bruton's tyrosine kinase (BTK) inhibitor being jointly developed by Janssen and Pharmacyclics, Inc. for the treatment of B-cell malignancies.

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