Wednesday, July 31, 2013

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."

Tuesday, July 30, 2013

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).

Monday, July 29, 2013

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.....

Friday, July 26, 2013

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 CRFurotensin Isauvagineurocortin 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.

Tuesday, July 23, 2013

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.

Monday, July 22, 2013

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."

Friday, July 19, 2013

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

Thursday, July 18, 2013

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


Wednesday, July 17, 2013

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 :

Tuesday, July 16, 2013

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 :  

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...

Monday, July 15, 2013

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....

Friday, July 12, 2013

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 :

Curcumin may protect premature infants' lungs

Thursday, July 11, 2013

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 :

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

Wednesday, July 10, 2013

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

Tuesday, July 9, 2013

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 :;jsessionid=A14E178EC5E6FC5D367A7C71FF0D30BC.d02t01

Smart anticancer 'nanofiber mesh'

Monday, July 8, 2013

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.

Thursday, July 4, 2013

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......

Wednesday, July 3, 2013

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