Clioquinol as anti-aging agent?

Clioquinol (5-Chloro-7-iodo-8-hydroxyquinoline), an 80-year old drug once used to treat diarrhea and other gastrointestinal disorders - can reverse the progression of Alzheimer's, Parkinson's and Huntington's diseases, something interesting and a serendipity again to the kitty of so many drugs...And the authors claims that Clioquinol is a very powerful inhibitor of clock-1, because clock-1 affects longevity in invertebrates and mice and hence can be used to treat the three age-dependent neurodegenerative diseases. Though detailed investigation is essential and one need to explain why, the drug was withdrawn from the market after being blamed for a devastating outbreak of subacute myelo-optic neuropathy (SMON) in Japan in the 1960s. Hope some solid conclusion will be arrived in the near future..

Source: http://www.ncbi.nlm.nih.gov/pubmed/18927074?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Olanzapine as long-acting injection (LAI) for acute and maintenance treatment of schizophrenia.?

Olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine) is one of the most commonly used drugs for atypical antipsychotics. Olanzapine has been approved by the FDA for the treatment of schizophrenia, acute mania in bipolar disorder, agitation associated with schizophrenia and bipolar disorder, and as maintenance treatment in bipolar disorder and psychotic depression. Zyprexa is Lilly’s top-selling drug, with sales of $4.2 billion last year.

Olanzapine's antipsychotic activity is mediated primarily by antagonism (blocking or inhibition) at dopamine receptors.

FDA required the manufacturers of all atypical antipsychotics to include a warning about the risk of hyperglycemia and diabetes with atypical antipsychotics.

Lilly is continuing to work with the agency on the new drug application (NDA). I think Lilly, has a come with a smart move like NDA, becoz., the FDA does not require any additional clinical trials for the continued review of the NDA. Per the agency's request, Lilly is preparing a proposed Risk Evaluation and Mitigation Strategy (REMS), which will be submitted in the near future. Hope this drug will not have the said side effects. A ray of hope for schizophrenia patients ? time will tell the story, best of luck Lilly....

New Benzothiazepine test to catch sports cheats ?

Though there are many tests for drugs (performance enhancers) for the sportpersons, they will try to use the drugs (wherein there are no tests to prove them guilty). Thanks to German research team who have come up with a new test. I am sure this test will try to combat the 'emerging drugs' and bring a sactity to the sport world.

The test detects a core chemical structure belonging to a class of compounds called benzothiazepines. These compounds stabilise protein channels that would otherwise "leak" calcium from muscle cells during strenuous exercise. Calcium is needed for muscle contraction and this "leaking" effect weakens the contractions and is a causal factor in muscle fatigue.

JTV-519 and S-107, benzothiazepines currently in development for the treatment of heart abnormalities, are known to increase endurance in mice. Although they have not yet entered human clinical trials, both can be detected using the test.

As soon as these drugs enter human clinical trials, there is a huge potential for them to be m isused in sports. This preventive research lets us prepare before these compounds are officially launched, says Mario Thevis, (lot of work done by his group in the spectroscopy field) Director of the Center for Preventive Doping Research at the German Sport University of Cologne, Germany, who led the research. The advantage of high resolution mass spectrometry, JTV-519 and S-107 can be detected in spiked urine at concentrations as low as 0.1 nanograms/ml. And hope they will try to achieve the detailed study of the metabolites also, which will further substantaite the evidence...More...

Mechanism of synthesizing estrogen visualized.....

Dr. Ghosh lab, has determined the structures of all three of the enzymes (aromatase, sulfatase and 17beta-hydroxysteroid dehydrogenase type 1) involved in controlling estrogen levels that can serve as drug targets for estrogen-dependent tumors in breast cancer. It s really interesting now as the structures of all three key enzymes implicated in estrogen-dependant breast cancers are known, one can have the drugs those can target these three enzymes. Hope with the help of molecular modelling, the goal to have a personalized cocktail of inhibitors customized to the specific treatment needs of each patient can be achieved in the days to come. Hats off to Dr.Ghosh and co workers and wish them to achieve the next target i.e., chemical mechanism involved in the conversion of androgens to estrogens. Once they achieve the next target, hope we will have more Aromatase inhibitor drugs with reduced side effects.....

Happy new Year 2009

Wish you all, A happy, prosperous and peaceful New Year-2009.

Nobel Prize in Chemistry 2008: Who won it and why?

Nobel Prize for Chemistry 2008 to Osamu Shimomura (USA), Martin Chalfie (USA) and Roger Y. Tsien (USA) for the "discovery and development of the green fluorescent protein, GFP". If interested watch the BBC documentary.

A new experimental drug "antagomir" (antisense oligonucleotide) as an anti- miR-21 agent..

MicroRNAs are small scraps of RNA comprising around 20 nucleotides and it is only recently that scientists have discovered their power which is they can regulate the expression (switching on and off) of a large number of human genes (they are like "master controllers"). And also these are the culprits (when microRNAs don't appear in the right place at the right time within cells) for diseases such as cancer, viral infections, inflammatory diseases and metabolic disorders. The potential to use them as targets for drugs is obvious and possibly explains why this is one of the fastest growing areas of development for new drugs and treatments.

Scientists already knew that microRNA was involved in switching genes on and off in the heart, but the underlying mechanisms and how they relate to the development of particular types of heart disease and their potential as drug targets were still relatively unknown.

Thum and colleagues discovered that miR-21 was expressed in the heart's fibroblast cells (cells that make the scaffolding of collagen or connective tissue that hold the shape of the organ) and were in greater numbers in lab mice bred to have heart failure and also in human tissue from patients who had heart failure.

In this study they showed that increasing expression of miR-21 changed the way that signals behaved in a previously unknown stress response pathway that involved the gene sprouty-1 and the MAP-kinase signaling pathway. In turn, increasing the activity of the MAP-kinase pathway led to a number of signs of heart failure, such as enhanced fibroblast survival, increased secretion of factors like fibroblast growth factor, tissue scarring (fibrosis), and cardiac dysfunction including cellular hypertrophy.

The researchers proved they could administer anti-miR-21 effectively to the heart by monitoring it with fluorescence staining. Then, in a mouse transaortic constriction model of human heart failure, they showed that anti-miR-21 silenced increased expression of miR-21 and corrected downstream changes in sprouty-1 and MAP-kinase signaling.

The interesting thing is their conclusion : Anti-miR-21, showed the most statistically significant improvement in the heart failure mouse model when given before induction of heart failure and for as long as three weeks afterward and it might be possible to target entire disease pathways with one drug. Contrats Dr. Thomas Thum.

A Deep Insight into the World Gene Therapy Market

A new market research report related to the Biotechnologies and Genetics industry about the trends in "antisense drugs".....

Non ulcerogenic new antiinflammatory drugs ?

When we see the presently available NSAIDs, most of them have ulcerogenicity as one of the common side effect. Ulcerogenicity can be explained by the metabolism of Arachidonic acid into various metabolites. Most of the drugs (NSAIDs) act by inhibiting the prostaglandins. But some of the prostaglandins are essential as cytoprotective layer and hence selective inhibitors of Cyclooxygenase –II (COX-II) and 5-LO (Lipoxygenase) are better tolerable and hence we can call these drugs as non ulcerogenic NSAIDs. Though these 2 enzymes (COX-II and 5-LO) were the targets of many drug discovers (as for as my knowledge goes, 1996-98 there were many papers regarding the selective inhibitors).

Now Oliver Werz and co workers have come with some new compounds 2-(4-(biphenyl-4-ylmethylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (with some structural variations like α substitution with extended n-alkyl or bulky aryl substituents and concomitant replacement of the 2,3-dimethylaniline by a biphenyl-4-yl-methane-amino residue) a derivative of pirinixic acid [PA, 2-(4-chloro-6-(2,3-dimethylphenylamino) pyrimidin-2-ylthio)acetic acid.

Significance of this research is the, less pronounced inhibition of cyclooxygenases-1/2. Taken together, these pirinixic acid derivatives constitute a novel class of dual mPGES-1/5-LO inhibitors with a promising pharmacologial profile and a potential for therapeutic use. More……

Iron complex mimics soil bacteria .....

Is there any synthetic chemical that acts, like a soil bacteria and there by degrade the aromatic compounds?. Now Prof. Lawrence Jr., and his group has come out with an interesting “synthetic non-heme iron complex “-that is able to catalyse the reaction.

The natural method for the degradation of aromatic compounds starts with the cis-dihydroxylation of an aromatic double bond by non-heme iron enzymes and the best known of these enzymes is naphthalene 1,2-dioxygenase (NDO), which catalyses the conversion of naphthalene to cis-(1R,2S)-1,2-dihydro-1,2-naphthalenediol. Although catalysts, those able to cis-hydroxylate olefin double bonds are known, the significance of this research is that a “synthetic catalyst which could carry out the same reaction on aromatic double bonds”.

Prof. Que, used a complex which had previously been successful in the cis-dihydroxylation of olefins, [FeII(TPA)(NCMe)2](OTf)2 [where TPA = tris(2-pyridylmethylamine)], using H2O2 as the oxidant. Interestingly the major of the identified four products (cis-diol), is identical to that produced in the enzyme-catalysed reaction. They also carried out mechanistic studies and found that the process is assisted by water. Though further studies are essential to substantiate the biomimetic catalysis of oxidations (previously carried out by enzymes). Hope this research will have its influence, in the areas like drug discovery, synthetic chemistry and environment issues…..