Promising chronic pain drug developed

4a,9-dihydroxy-7a-(hydroxymethyl)-3-methyl-2,3,4,4a,5,6-hexahydro-1H-4,12-methanol benzofuro[3,2-e]isoquinoline-7(7aH)-one (UMB 425)

Spotlighted in a recent issue of ACS Chemical Neuroscience, the compound, known as UMB 425, is as strong as morphine, but displays diminished tolerance over time with no obvious toxic effects.

"UMB 425 is a breakthrough in the development of therapeutics to treat chronic pain," says Coop. "Unlike other drugs developed to act on only one biological target, UMB 425 acts on two different opioid receptors in the body. When activated at the same time, these receptors work together to provide pain relief and slow the body's development of tolerance to the drug. This diminished tolerance allows a lower dose of the opioid to be administered for a longer time period, while still achieving the same level of pain relief."

For individuals living with chronic pain, either as a result of injury or disease such as arthritis, opioids are the standard treatment. But as the dosage increases to offset the body's tolerance to their effects, opioids cause a number of adverse effects, including constipation, nausea, drowsiness, and dizziness. The unique dual-profile of UMB 425 -- made possible through Coop's collaborations with Alexander MacKerell, PhD, professor in PSC and director of the School's Computer Aided Drug Design Center, and Maureen Kane, PhD, assistant professor in PSC and co-director of the School's Mass Spectrometry Facility -- provides both pain relief as well as diminished tolerance in one drug.

"Historically, medicinal chemists have developed drugs aimed at only one biological target," says Coop. "However, two drugs administered together have the potential to metabolize differently in different individuals, as well as affect patients' adherence to both drugs. A single compound that is able to provide both pain relief and diminished tolerance has the advantage of a defined ratio that we can optimize to ensure patients receive the maximum pain relief, while experiencing minimum adverse effects."

Ref : http://pubs.acs.org/doi/pdf/10.1021/cn4000428

Promising chronic pain drug developed

Eating whole fruits linked to lower risk of Type 2 diabetes

Eating more whole fruits, particularly blueberries, grapes, and apples, was significantly associated with a lower risk of type 2 diabetes, according to a new study led by Harvard School of Public Health (HSPH) researchers. Greater consumption of fruit juices was associated with a higher risk of type 2 diabetes. The study is the first to look at the effects of individual fruits on diabetes risk.

Eating whole fruits linked to lower risk of Type 2 diabetes

Unexpected use of former cancer drug, Zebularine...

Researchers at Lund University have unexpectedly discovered that an old cancer drug can be used to prevent rejection of transplanted tissue. The researchers now have high hopes that their discovery could lead to new treatments for both transplant patients and patients with autoimmune diseases.

"Our group were studying the effects of the old tumour drug Zebularine, (see structure) developed in the USA in the 1960s, and by chance we discovered that it had completely unexpected effects on the immune system," says Leif Salford, Senior Professor of Neurosurgery.

"It turned out that Zebularine has the ability to subdue the reaction of the body's immune system. This could be important in situations where tissue or organs are transplanted. We also think it could be used to curb the body's attacks on its own tissue in autoimmune diseases, for instance type 1 diabetes or rheumatoid arthritis," says Dr Nittby.

In studies on animals, the researchers used rats that were made diabetic. The researchers transplanted the islets of Langerhans  cell groups in the pancreas producing insulin -- from healthy rats from another kind of rat into those with diabetes. The diabetic rats were divided into two groups; one group were treated with Zebularine and the other, the control group, did not receive any treatment. The diabetic rats that were treated with Zebularine survived for a significantly longer period than the untreated rats.

"It is very interesting that we only treated them with Zebularine for two weeks, but the effects of the treatment could be observed throughout the 90-day follow-up period.

"The findings are very exciting and are a sign that the immune system was not just generally suppressed, but that the treatment was more targeted. Neither did we see any signs of side-effects," said Dr Nittby.

The researchers are now working intensively to further refine the treatment. The next step is to teach certain cells in the immune system -- the dendritic cells -- to accept certain specific proteins using the Zebularine treatment. This would mean that the treatment could be targeted even more.

Unexpected use of former cancer drug

Drug reduces hospitalizations and cost of treating young children with sickle cell anemia

The study is the largest ever focusing on the economic impact of the drug hydroxyurea (see structure below)

 in children with the inherited blood disorder. The result supports expanded use of the drug to extend the length and quality of life for sickle cell anemia patients of all ages, said Winfred Wang, M.D., a member of the St. Jude Department of Hematology and principal investigator of the multicenter federally funded trial known as BABY HUG.

"We estimate that hydroxyurea cut overall annual medical expenses about $3,000 for each patient by helping patients avoid disease complications that require inpatient hospital care," said Wang, who is first and corresponding author of the Pediatrics study. "We expect those savings will grow along with patients, whose symptoms often increase in severity and frequency as they age."

About 100,000 individuals in the U.S. and millions worldwide have sickle cell disease, which leaves them at risk for premature death and disability. The disease is the most common genetic disorder affecting African-American individuals, but those from other ethnic and racial backgrounds also inherit mutations in the hemoglobin gene. The mutations result in blood cells that are prone to assuming the sickled shape that gives the disease its name and that leave patients at increased risk for episodes of acute pain, stroke, organ damage and other complications.

Drug reduces hospitalizations and cost of treating young children with sickle cell anemia

Scientists fish for new epilepsy model and reel in potential drug

According to new research on epilepsy, zebrafish have certainly earned their stripes. Results of a study in Nature Communications suggest that zebrafish carrying a specific mutation may help researchers discover treatments for Dravet syndrome (DS), a severe form of pediatric epilepsy that results in drug-resistant seizures and developmental delays.

Scientists fish for new epilepsy model and reel in potential drug

Synthetic polymer could stop the spread of HIV

The researchers created the large molecule with several sugar molecules, known as glycopolymers (Glycopolymer is synthetic polymer with pendant carbohydrates). By using different sugars attached to the macromolecule in solution, the scientists were able to investigate which sugar molecules were the most effective in inhibiting the potential binding of the virus.

They then measured how the designed macromolecules compete with the virus to bind to the dendritic cells of the immune system at different concentrations.

"These are preliminary but encouraging results for potentially preventing the spread of the HIV by sexual contact," said Dr Remzi Becer from Queen Mary's School of Engineering and Materials Science.

"We've shown that our synthetic molecule binds to the immune cell, which in turn blocks the virus from attaching and entering. The precisely designed macromolecules could be an ingredient of a condom cream or vaginal gel to act as a physical barrier from allowing the virus into the body."

Dr Becer added: "While this isn't a cure for HIV, it is a novel approach that could dramatically slow down the spread of HIV by sexual contact, and a model that could be replicated to treat other sexually transmitted diseases."

Ref : http://onlinelibrary.wiley.com/doi/10.1002/marc.201300439/abstract

Synthetic polymer could stop the spread of HIV

Alzheimer's 'missing link' found: Promising target for new drugs

Yale School of Medicine researchers have discovered a protein that is the missing link in the complicated chain of events that lead to Alzheimer's disease, they report in the Sept. 4 issue of the journal Neuron. Researchers also found that blocking the protein with an existing drug can restore memory in mice with brain damage that mimics the disease.

Ref : http://dx.doi.org/10.1016/j.neuron.2013.06.036

Alzheimer's 'missing link' found: Promising target for new drugs

AstraZeneca and Bristol-Myers Squibb resubmit Dapagliflozin New Drug Application for the treatment of type 2 diabetes in the U.S

In continuation of my update on Dapagliflozin

AstraZeneca and Bristol-Myers Squibb resubmit Dapagliflozin New Drug Application for the treatment of type 2 diabetes in the U.S

FDA Advisory Committee Unanimously Recommends Approval Of Bayer's Riociguat In Two Pulmonary Hypertension Indications

We know that, Riociguat is (BAY 63-2521) is a novel drug that is in clinical development by Bayer. It is a stimulator ofsoluble guanylate cyclase (sGC). At the moment Phase III clinical trials investigate the use of riociguat as a new approach to treat two forms of pulmonary hypertension (PH): chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Riociguat constitutes the first drug of a novel class of sGC stimulators.

FDA Advisory Committee Unanimously Recommends Approval Of Bayer's Riociguat In Two Pulmonary Hypertension Indications

Drug used for blood cancers may stop spread of breast cancer cells

In continuation of my update on Decitabine

A drug used to treat blood cancers may also stop the spread of invasive breast cancer, researchers at Mayo Clinic in Florida have discovered. Their study, published online in Breast Cancer Research, found that in the lab and in animals, the drug decitabine turns on a gene coding for protein kinase D1 (PRKD1) that halts the ability of cancer cells to separate from a tumor and spread to distant organs.

Drug used for blood cancers may stop spread of breast cancer cells

Ref : http://breast-cancer-research.com/content/15/2/R66

Study: Type 2 diabetic patients treated with DPP-4 linagliptin experience reductions in blood glucose levels

Data published in The Lancet showed that elderly people with Type 2 Diabetes (T2D) treated for 24 weeks with the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin, marketed by Boehringer Ingelheim and Eli Lilly and Company, experienced significant reductions in blood glucose levels (HbA1c) compared with those receiving placebo. In addition, the overall safety and tolerability profile of linagliptin was similar to placebo, with no significant difference in hypoglycaemia.

Study: Type 2 diabetic patients treated with DPP-4 linagliptin experience reductions in blood glucose levels

Watermelon juice relieves post-exercise muscle soreness

Encarna Aguayo and colleagues cite past research on watermelon juice's antioxidant properties and its potential to increase muscle protein and enhance athletic performance. But scientists had yet to explore the effectiveness of watermelon juice drinks enriched in L-citrulline. Aguayo's team set out to fill that gap in knowledge.

They tested natural watermelon juice, watermelon juice enriched in L-citrulline (ABOVE STRUCTURE) and a control drink containing no L-citrulline on volunteers an hour before exercise. Both the natural juice and the enriched juice relieved muscle soreness in the volunteers. L-citrulline in the natural juice (unpasteurized), however, seemed to be more bioavailable -- in a form the body could better use, the study found.

Watermelon juice relieves post-exercise muscle soreness

Combined therapy could repair and prevent damage in Duchenne muscular dystrophy, study suggests

Results from a clinical trial of eteplirsen, {RNA, [P-deoxy-P-(dimethylamino)](2',3'-dideoxy-2',3'-imino-2',3'-seco)(2'a→5')(C-m5U-   C-C-A-A-C-A-m5U-C-A-A-G-G-A-A-G-A-m5U-G-G-C-A-m5U-m5U-m5U-C-m5U-A-G),    5'-[P-[4-[[2-[2-(2-hydroxyethoxy) ethoxy]ethoxy] carbonyl]-1-piperazinyl]-N,N-   dimethylphosphonamidate]}  a drug designed to treat Duchenne muscular dystrophy, suggest that the therapy allows participants to walk farther than people treated with placebo and dramatically increases production of a protein vital to muscle growth and health. The study, led by a team in The Research Institute at Nationwide Children's Hospital, is the first of its kind to show these results from an exon-skipping drug -- a class of therapeutics that allows cells to skip over missing parts of the gene and produce protein naturally....

Combined therapy could repair and prevent damage in Duchenne muscular dystrophy, study suggests

Ref http://onlinelibrary.wiley.com/doi/10.1002/ana.23982/abstract

New approach in the treatment of breast cancer

Scientists at the MedUni Vienna, in collaboration with a working group led by Nancy Hynes at the University of Basel, have discovered a new approach in the treatment of breast cancer: an international team involving the Clinical Institute of Pathology at the MedUni Vienna has been able to demonstrate the activation of a receptor, the Ret protein (Rearranged during transfection), on the surface of breast cancer cells. Increased levels of this protein are associated with a lower likelihood of survival for breast cancer patients.

Ref : http://onlinelibrary.wiley.com/doi/10.1002/emmm.201302625/abstract

Read more about RET Inhibitors at : http://www.cancercommons.org/tag/ret-inhibitors/

New approach in the treatment of breast cancer

GLENMARK-A new way for a new world « New Drug Approvals

Undiminished zest..

“Every year we expect two more molecules to get into clinical trials,” says Saldanha, his zest undiminished by past failures. “In 2008, in a span of one or two quarters, our entire pipeline pretty much got wiped out, but we never lost our commitment and passion.” At that time its most advanced molecule, oglemilast, used for treating patients with chronic obstructive pulmonary disease, had to be abandoned when its Phase IIb trials produced unsatisfactory results. It also had to suspend clinical development of GRC 6211, a compound for treating osteoarthritis pain, because of side effects.

GLENMARK-A new way for a new world « New Drug Approvals