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.
Med-Chemist : "Quintessential Medicinal Chemistry"
Friday, August 30, 2013
Wednesday, August 28, 2013
Watermelon juice relieves post-exercise muscle soreness
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.
Tuesday, August 27, 2013
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....
Monday, August 26, 2013
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.
Read more about RET Inhibitors at : http://www.cancercommons.org/tag/ret-inhibitors/
Sunday, August 25, 2013
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.
Friday, August 23, 2013
New treatment for brittle bone disease found
We know that, Risedronic acid (see structure) (INN) or risedronate sodium (USAN) is a bisphosphonate used to strengthen bone, treat or prevent osteoporosis, and treat Paget's disease of bone. It is produced and marketed by Warner Chilcott, Sanofi-Aventis, and in Japan by Takeda under the trade names Actonel, Atelvia, and Benet. It is also available in a preparation that includes a calcium carbonate supplement, asActonel with Calcium.
Osteogenesis imperfecta (OI and sometimes known as brittle bone disease, or "Lobstein syndrome") is a congenital bone disorder. People with OI are born with defective connective tissue, or without the ability to make it, usually because of a deficiency ofType-I collagen. This deficiency arises from an amino acid substitution of glycine to bulkier amino acids in the collagen triple helixstructure. The larger amino acid side-chains create steric hindrance that creates a bulge in the collagen complex, which in turn influences both the molecular nanomechanics as well as the interaction between molecules, which are both compromised.[3] As a result, the body may respond by hydrolyzing the improper collagen structure. If the body does not destroy the improper collagen, the relationship between the collagen fibrils and hydroxyapatite crystals to form bone is altered, causing brittleness.[4] Another suggested disease mechanism is that the stress state within collagen fibrils is altered at the locations of mutations, where locally larger shear forces lead to rapid failure of fibrils even at moderate loads as the homogeneous stress state found in healthy collagen fibrils is lost.[3]These recent works suggest that OI must be understood as a multi-scale phenomenon, which involves mechanisms at the genetic, nano-, micro- and macro-level of tissues.
Thursday, August 22, 2013
Wednesday, August 21, 2013
New designer compound JQ1, treats heart failure by targeting cell nucleus
Researchers from Case Western Reserve University School of Medicine and the Dana-Farber Cancer Institute have made a fundamental discovery relevant to the understanding and treatment of heart failure -- a leading cause of death worldwide. The team discovered a new molecular pathway responsible for causing heart failure and showed that a first-in-class prototype drug, JQ1, (see structure) blocks this pathway to protect the heart from damage.
In contrast to standard therapies for heart failure, JQ1 works directly within the cell's command center, or nucleus, to prevent damaging stress responses. This groundbreaking research lays the foundation for an entirely new way of treating a diseased heart. The study is published in the August 1 issue of Cell.
"As a practicing cardiologist, it is clear that current heart failure drugs fall alarmingly short for countless patients. Our discovery heralds a brand new class of drugs which work within the cell nucleus and offers promise to millions suffering from this common and lethal disease," said Saptarsi Haldar, MD, senior author on the paper, assistant professor of medicine at Case Western Reserve and cardiologist at University Hospitals Case Medical Center.
Heart failure occurs when the organ's pumping capacity cannot meet the body's needs. Existing drugs, most of which block hormones such as adrenaline at the cell's outer surface, have improved patient survival. Unfortunately, several clinical studies have demonstrated that heart failure patients taking these hormone-blocking drugs still succumb to high rates of hospitalization and death. Leveraging a new approach, the research team turned their attention from the cell's periphery to the nucleus -- the very place that unleashes sweeping damage-control responses which, if left unchecked, ultimately destroy the heart.
The team found that a new family of genes, called BET bromodomains, cause heart failure because they drive hyperactive stress responses in the nucleus. Prior research linking BET bromodomains to cancer prompted the laboratory of James Bradner, MD, the paper's senior author and a researcher at the Dana-Farber, to develop a direct-acting BET inhibitor, called JQ1. In models of cancer, JQ1 functions to turn off key cancer-causing genes occasionally prompting cancer cells to "forget" they are cancer. In models of heart failure, JQ1 silences genetic actions causing enlargement of and damage to the heart even in the face of overwhelming stress.
"While it's been known for many years that the nucleus goes awry in heart failure, potential therapeutic targets residing in this part of the cell are often dubbed as 'undruggable' given their lack of pharmacological accessibility," said Jonathan Brown, MD, cardiologist at Brigham and Women's Hospital and co-first author on the paper. "Our work with JQ1 in pre-clinical models shows that this can be achieved successfully and safely."
Scripps Florida Scientists Devise New Way to Dramatically Raise RNA Treatment Potency
"We're trying to make tools that can target any RNA motif," said Matthew Disney, a TSRI associate professor who authored the research with a research associate in his lab, Lirui Guan. "This study completely validates our design -- it validates that our compound targets the desired RNA sequence in a complex cellular environment that contains many hundreds of thousands of RNAs."
While targeting DNA has been used as a therapeutic strategy against cancer, few similar approaches have been attempted for disease-associated RNAs.
In the new study, the scientists created a small molecule that binds to the genetic defect in RNA that causes myotonic dystrophy type 1 and improves associated defects in cell culture.
Myotonic dystrophy type 1 involves a type of RNA defect known as a "triplet repeat," a series of three nucleotides repeated more times than normal in an individual's genetic code. In this case, the repetition of the cytosine-uracil-guanine (CUG) in the RNA sequence leads to disease by binding to a particular protein, MBNL1, rendering it inactive and resulting in a number of protein-splicing abnormalities.
To achieve the increase in the drug candidate's potency, Disney and his colleagues attached a reactive molecule (a derivative of chlorambucil, (see structure below) a chemotherapy drug that has been used to treatment a form of leukemia) to the small molecule they had identified. As a result, the new compound not only binds to the target, it becomes a permanent part of the target -- as if it were super glued to it, Disney said. Once attached, it switches off the CUG defect and prevents the cell from turning it back on.
Disney was surprised at the approximately 2,500-fold improvement in potency with the new approach.
"I was shocked by the increase," he said. "This takes the potency into the realm where one would like to see if the compound were to have real therapeutic potential."
As a result, the new compound, known as 2H-4-CA, is the most potent compound known to date that improves DM1-associated splicing defects. Importantly, 2H-4-CA does not affect the alternative splicing of a transcript not regulated by MBNL1, demonstrating selectivity for the CUG repeat and suggesting that it might have minimal side effects. "We can now use this approach to attach reactive molecules to other RNA targeted small molecules," Disney said.
The reactive molecule model also provides a potentially general method to identify cellular targets of RNA-directed small molecules. Such probes could also identify unintended targets, information that could be used to design and identify compounds with improved selectivity in an approach similar to activity-based profiling, Disney said.
Tuesday, August 20, 2013
Scientists ID compounds that target amyloid fibrils in Alzheimer's, other brain diseases
The UCLA researchers, led by David Eisenberg, director of the UCLA-Department of Energy Institute of Genomics and Proteomics and a Howard Hughes Medical Institute investigator, report the first application of this technique in the search for molecular compounds that bind to and inhibit the activity of the amyloid-beta protein responsible for forming dangerous plaques in the brain of patients with Alzheimer's and other degenerative diseases.
o identify natural and synthetic compounds that might prevent the aggregation and toxicity of amyloid fibrils. Such studies have revealed that polyphenols, naturally occurring compounds found in green tea and in the spice turmeric, can inhibit the formation of amyloid fibrils. In addition, several dyes have been found to reduce amyloid's toxic effects, although significant side effects prevent them from being used as drugs.
Armed with a precise knowledge of the atomic structure of the amyloid-beta protein, Jiang, Eisenberg and colleagues conducted a computational screening of 18,000 compounds in search of those most likely to bind tightly and effectively to the protein.
Those compounds that showed the strongest potential for binding were then tested for their efficacy in blocking the aggregation of amyloid-beta and for their ability to protect mammalian cells grown in culture from the protein's toxic effects, which in the past has proved very difficult. Ultimately, the researchers identified eight compounds and three compound derivatives that had a significant effect.
While these compounds did not reduce the amount of protein aggregates, they were found to reduce the protein's toxicity and to increase the stability of amyloid fibrils a finding that lends further evidence to the theory that smaller assemblies of amyloid-beta known as oligomers, and not the fibrils themselves, are the toxic agents responsible for Alzheimer's symptoms.
The researchers hypothesize that by binding snugly to the protein, the compounds they identified may be preventing these smaller oligomers from breaking free of the amyloid-beta fibrils, thus keeping toxicity in check...
Monday, August 19, 2013
GlaxoSmithKline receives CHMP positive opinion for REVOLADE
In continuation of my update on Eltrombopag
Eltrombopag (codenamed SB-497115-GR) is a medication that has been developed for conditions that lead to thrombocytopenia (abnormally low platelet counts). It is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of the hormone thrombopoietin. Eltrombopag was discovered as a result of research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals. Designated an orphan drugin the USA and European Union, it is being manufactured and marketed by GlaxoSmithKline under the trade name Promacta in the USA and will be marketed as Revolade in the EU. Eltrombopag was approved by the U.S. Food and Drug Administration on November 20, 2008....
Friday, August 16, 2013
Rapamycin: Limited anti-aging effects
In continuation of my update on Rapamycin
The drug rapamycin is known to increase lifespan in mice. Whether rapamycin slows down aging, however, remains unclear. A team of researchers from the German Center for Neurodegenerative Diseases (DZNE) and the Helmholtz Zentrum München has now found that rapamycin extends lifespan -- but its impact on aging itself is limited. The life-extending effect seems to be related to rapamycin's suppression of tumors, which represent the main causes of death in these mouse strains....
The drug rapamycin is known to increase lifespan in mice. Whether rapamycin slows down aging, however, remains unclear. A team of researchers from the German Center for Neurodegenerative Diseases (DZNE) and the Helmholtz Zentrum München has now found that rapamycin extends lifespan -- but its impact on aging itself is limited. The life-extending effect seems to be related to rapamycin's suppression of tumors, which represent the main causes of death in these mouse strains....
Thursday, August 15, 2013
Teduglutide offers relief for patients with short-bowel syndrome
In continuation of my update on Teduglutide
Teduglutide (brand names Gattex and Revestive) is a 36-membered polypeptide and glucagon-like peptide-2 analog that is used for the treatment of short bowel syndrome. It works by promoting mucosal growth and possibly restoring gastric emptying and secretion. In Europe it is marketed under the brand Revestive by Nycomed. It was approved by the United States under the name Gattex on December 21, 2012...
Wednesday, August 14, 2013
Chelsea Therapeutics Announces FDA Acceptance of Northera (droxidopa) NDA Resubmission
In continuation of my update on droxidopa.....
Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) today announced that the U.S. Food and Drug Administration (FDA) has acknowledged receipt of the New Drug Application (NDA) resubmission seeking approval to market NORTHERA(TM) (droxidopa), an orally active synthetic precursor of norepinephrine, for the treatment of symptomatic neurogenic orthostatic hypotension (NOH) in patients with primary autonomic failure (Parkinson's disease, multiple system atrophy and pure autonomic failure), dopamine beta hydroxylase deficiency and non-diabetic autonomic neuropathy. The FDA has deemed the resubmission a complete response to its March 28, 2012 Complete Response Letter and assigned a new Prescription Drug User Fee Act (PDUFA) goal date of January 3, 2014.
Tuesday, August 13, 2013
Cheaper anti-cancer drug as effective as expensive drug in treating most common cause of blindness in older adults
Results of a two-year trial, led by Queen's scientist Professor Usha Chakravarthy, and published in The Lancet today (Friday 19 July), show that two drug treatments Lucentis and Avastinare equally effective in treating neovascular or wet age-related macular degeneration (wet AMD)....
Cheaper anti-cancer drug as effective as expensive drug in treating most common cause of blindness in older adults
Monday, August 12, 2013
New drugs to find the right target to fight Alzheimer's disease
A favorite Alzheimer's target: gamma secretase
The two next-generation classes of compound that are currently in clinical trials target an enzyme that cuts APP, known as gamma secretase. Until now, our understanding of the mechanism involved has been lacking. But with this work, the EPFL researchers were able to shed some more light on it by determining how the drug compounds affect gamma secretase and its cutting activity.
In most forms of Alzheimer's, abnormally large quantities of the long amyloid peptide 42 -- named like that because it contains 42 amino acids are formed. The drug compounds change the location where gamma secretase cuts the APP protein, thus producing amyloid peptide 38 instead of 42, which is shorter and does not aggregate into neurotoxic plaques.
Compared to previous therapeutic efforts, this is considerable progress. In 2010, Phase III clinical trials had to be abandoned, because the compound being tested inhibited gamma-secretase's function across the board, meaning that the enzyme was also deactivated in essential cellular differentiation processes, resulting to side-effects like in gastrointestinal bleeding and skin cancer.
"Scientists have been trying to target gamma secretase to treat Alzheimer's for over a decade," explains Patrick Fraering, senior author on the study and Merck Serono Chair of Neurosciences at EPFL. "Our work suggests that next-generation molecules, by modulating rather than inhibiting the enzyme, could have few, if any, side-effects. It is tremendously encouraging."
Friday, August 9, 2013
Necrostatin-1 counteracts aluminum's neurotoxic effects
we know that, Necrostatin-1 inhibits necroptosis, a non-apoptotic cell death pathway. Inhibits the loss of mitochondrial membrane potential in TNFα-treated Jurkat cells (EC50=490 nM). Does not inhibit FAS-induced apoptosis and has no effect on apoptotic morphology. It displays a pronounced protective effect in a mouse model of ischemic brain injury and inhibits myocardial cell death. Inhibits RIP1 kinase the key upstream kinase involved in the activation of necroptosis (EC50=180nM).
Ivestigators have linked aluminum accumulation in the brain as a possible contributing factor to neurodegenerative disorders such as Alzheimer's disease. A new study published in Restorative Neurology and Neuroscience sheds light on the mechanism underlying aluminum-induced neuronal cell death and identifies necrostatin-1 as a substance which counteracts several of aluminum's neurotoxic effects.
Ref : http://iospress.metapress.com/content/h81617j3542x6487/?p=cfdaeabe671d4941ba8ae36ae55c6c5f&pi=0
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.
Thursday, August 8, 2013
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.
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.
Wednesday, August 7, 2013
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 ....Tuesday, August 6, 2013
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....
Monday, August 5, 2013
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.
Friday, August 2, 2013
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....