New Optical Technique Provides Easy Way To Detect TB Bacteria In Fluids
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Med-Chemist : "Quintessential Medicinal Chemistry"
Saturday, October 10, 2009
Telomerase & Telomerase inhibition.......
When I read about the Nobel prize in Medicine, was really excited because the scientists who discovered the enzyme telomerase got the Nobel prize for the year 2009 and the reason for this is simple and obvious....
When I was working with my previous company (Innovasynth Technologies Limited, Khopoli), I had opportunity to learn lots of things (from Dr. Sergei Gryaznov of Geron Corporation) about the drugs with Telomerase inhibition activity. As for as my knowledge goes, there are many companies working on these class of compounds and hope in the days to come there will be many drugs from this class of compounds and antisense drugs.
About Telomerase :
Telomerase, is an enzyme that adds specific DNA sequence repeats to the 3' end of DNA strands in the telomerase regions, which are found at the ends of eukaryotic chromosomes. The telomeres contain condensed DNA material, giving stability to the chromosomes. The enzyme is a reverse transcriptase that carries its own RNA molecule. Though the existence of a compensatory shortening of telomere (telomerase) mechanism, was first predicted by Soviet biologist Alexey Olovnikov (1973), who also suggested the Telomere hypothesis of ageing and the Telomere relations to cancer. Carol Greider and Elizabeth Blackburn in 1985, discovered telomerase together with Jack Szostak. Greider and Blackburn have been awarded the Nobel Prize in Physiology or Medicine. Congrats for this remarkable achievement.
Telomerase inhibitors :
To safeguard against cancer, adult cells keep track of how many times that they have multiplied, and once they have reached a pre-set limit — often around 80 divisions — they die. Telomerase interferes with this record keeping. So if one can find a drug or gene therapy that interferes with telomerase, it could fight the unchecked growth of cancer cells. As per the claim by lead researcher (Mark Muller), 90% all cancer cells are telomerase rich. Geron corporation, is developing modified DNA molecule (for which Innovasynth, has tie up with Geron to provide the intermediate amidites). The oligonucleotides, which target the template region, or active site, of telomerase. Geron's work has focused oligonucleotides (GRN163 and GRN163L,) and as per the claim by the company, both of them have demonstrated highly potent telomerase inhibitory activity at very low concentrations in biochemical assays, various cellular systems and animal studies. Interestingly these compounds are direct enzyme inhibitors, not antisense compounds and smaller than typical antisense compounds or other oligonucleotide drug candidates. Both compounds use a special thiophosphoramidate chemical backbone and the company is hopeful of convincing clinical trial results. All the best...
Ref : 1. http://nobelprize.org/nobel_prizes/medicine/laureates/2009/press.html
2. http://www.geron.com/products/productinformation/cancerdrug.aspx
When I was working with my previous company (Innovasynth Technologies Limited, Khopoli), I had opportunity to learn lots of things (from Dr. Sergei Gryaznov of Geron Corporation) about the drugs with Telomerase inhibition activity. As for as my knowledge goes, there are many companies working on these class of compounds and hope in the days to come there will be many drugs from this class of compounds and antisense drugs.
About Telomerase :
Telomerase, is an enzyme that adds specific DNA sequence repeats to the 3' end of DNA strands in the telomerase regions, which are found at the ends of eukaryotic chromosomes. The telomeres contain condensed DNA material, giving stability to the chromosomes. The enzyme is a reverse transcriptase that carries its own RNA molecule. Though the existence of a compensatory shortening of telomere (telomerase) mechanism, was first predicted by Soviet biologist Alexey Olovnikov (1973), who also suggested the Telomere hypothesis of ageing and the Telomere relations to cancer. Carol Greider and Elizabeth Blackburn in 1985, discovered telomerase together with Jack Szostak. Greider and Blackburn have been awarded the Nobel Prize in Physiology or Medicine. Congrats for this remarkable achievement.
Telomerase inhibitors :
To safeguard against cancer, adult cells keep track of how many times that they have multiplied, and once they have reached a pre-set limit — often around 80 divisions — they die. Telomerase interferes with this record keeping. So if one can find a drug or gene therapy that interferes with telomerase, it could fight the unchecked growth of cancer cells. As per the claim by lead researcher (Mark Muller), 90% all cancer cells are telomerase rich. Geron corporation, is developing modified DNA molecule (for which Innovasynth, has tie up with Geron to provide the intermediate amidites). The oligonucleotides, which target the template region, or active site, of telomerase. Geron's work has focused oligonucleotides (GRN163 and GRN163L,) and as per the claim by the company, both of them have demonstrated highly potent telomerase inhibitory activity at very low concentrations in biochemical assays, various cellular systems and animal studies. Interestingly these compounds are direct enzyme inhibitors, not antisense compounds and smaller than typical antisense compounds or other oligonucleotide drug candidates. Both compounds use a special thiophosphoramidate chemical backbone and the company is hopeful of convincing clinical trial results. All the best...
Ref : 1. http://nobelprize.org/nobel_prizes/medicine/laureates/2009/press.html
2. http://www.geron.com/products/productinformation/cancerdrug.aspx
Friday, October 9, 2009
Wednesday, October 7, 2009
2009 Nobel Prize for Chemistry......
This year's (2009) Nobel Prize in Chemistry is awarded to Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath (from left to right respectively) for their studies of the structure and function of the ribosome.
The Nobel Prize in Chemistry for 2009 awards studies of one of life's core processes: the ribosome's translation of DNA information into life. Ribosomes produce proteins, which in turn control the chemistry in all living organisms. As ribosomes are crucial to life, they are also a major target for new antibiotics. Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath for having showed what the ribosome looks like and how it functions at the atomic level. All three have used a method called X-ray crystallography to map the position for each and every one of the hundreds of thousands of atoms that make up the ribosome.
This year's three Laureates have all generated 3D models that show how different antibiotics bind to the ribosome. These models are now used by scientists in order to develop new antibiotics, directly assisting the saving of lives and decreasing humanity's suffering. One can read more details with the link.
Congratulations to all of them for this remarkable achievement. Its interesting to note that Dr. Medicinein 1968, its V.Ramakrishnan in the Science field.
Ref : http://nobelprize.org/nobel_prizes/chemistry/laureates/2009/
The Nobel Prize in Chemistry for 2009 awards studies of one of life's core processes: the ribosome's translation of DNA information into life. Ribosomes produce proteins, which in turn control the chemistry in all living organisms. As ribosomes are crucial to life, they are also a major target for new antibiotics. Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath for having showed what the ribosome looks like and how it functions at the atomic level. All three have used a method called X-ray crystallography to map the position for each and every one of the hundreds of thousands of atoms that make up the ribosome.
This year's three Laureates have all generated 3D models that show how different antibiotics bind to the ribosome. These models are now used by scientists in order to develop new antibiotics, directly assisting the saving of lives and decreasing humanity's suffering. One can read more details with the link.
Congratulations to all of them for this remarkable achievement. Its interesting to note that Dr. Medicinein 1968, its V.Ramakrishnan in the Science field.
Ref : http://nobelprize.org/nobel_prizes/chemistry/laureates/2009/
Tuesday, October 6, 2009
Minocycline for stroke patients?
Minocycline hydrochloride, also known as minocycline (right structure), is a broad spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bactriostatic antibiotic. As a result of its long half-life it generally has serum levels 2-4 times that of most other tetracyclines (150 mg giving 16 times the activity levels compared to 250 mg of tetracycline at 24–48 hours). It is primarily used to treat acne and other skin infections. Apart from the antibacterial activity, 'minocycline' is recognized as a DMARD (Disease-Modifying Anti-Rheumatic Drug) by the American College of Rheumatology, which recommends its use as a treatment for mild rheumatoid arthritis.
A recent study by the Dr. Cesar V. Borlongan (University of South Florida, USA) has lead to some interesting result, i.e., minocycline can be used to treat the stroke patients !. As per the claim by the researchers this drug might be a better option, when compared with the thrombolytic agent tPA (the only effective drug for acute ischemic stroke) and more over only 2 % of ischemic stroke patients benefit from this treatment due to its limited therapeutic window.
During a stroke, a clot prevents blood flow to parts of the brain, which can have wide ranging short-term and long-term implications. This study recorded the effect of intravenous minocycline in both isolated neurons and animal models after a stroke had been experimentally induced. At low doses it was found to have a neuroprotective effect on neurons by reducing apoptosis of neuronal cells and ameliorating behavioral deficits caused by stroke. The safety and therapeutic efficacy of low dose minocycline and its robust neuroprotective effects during acute ischemic stroke make it an appealing drug candidate for stroke therapy claims the researchers. Congrats for this interesting finding...
Ref : http://www.biomedcentral.com/1471-2202/10/126/abstract
A recent study by the Dr. Cesar V. Borlongan (University of South Florida, USA) has lead to some interesting result, i.e., minocycline can be used to treat the stroke patients !. As per the claim by the researchers this drug might be a better option, when compared with the thrombolytic agent tPA (the only effective drug for acute ischemic stroke) and more over only 2 % of ischemic stroke patients benefit from this treatment due to its limited therapeutic window.
During a stroke, a clot prevents blood flow to parts of the brain, which can have wide ranging short-term and long-term implications. This study recorded the effect of intravenous minocycline in both isolated neurons and animal models after a stroke had been experimentally induced. At low doses it was found to have a neuroprotective effect on neurons by reducing apoptosis of neuronal cells and ameliorating behavioral deficits caused by stroke. The safety and therapeutic efficacy of low dose minocycline and its robust neuroprotective effects during acute ischemic stroke make it an appealing drug candidate for stroke therapy claims the researchers. Congrats for this interesting finding...
Ref : http://www.biomedcentral.com/1471-2202/10/126/abstract
Sunday, October 4, 2009
Combination of Depagliflozin & Metaformin for type 2 diabatic ?
We knew that these two Depagliflozin (left) & Metaformin (right) compounds were being studied independently for type 2 diabetic condition. Dapagliflozin, an investigational compound, is a potential first-in-class SGLT2 inhibitor currently in Phase 3 trials under joint development as a once-daily oral therapy for the treatment of type 2 diabetes. SGLT2 inhibitors facilitate the elimination of glucose by the kidney, thereby returning serum glucose levels towards normal.A recent study (24-week phase 3 clinical study by Bristol-Myers Squibb Company and AstraZeneca) demonstrated that the investigational drug dapagliflozin, added to metformin, demonstrated significant mean reductions in the primary endpoint, glycosylated hemoglobin level (HbA1c) and in the secondary endpoint, fasting plasma glucose (FPG) in patients with type 2 diabetes inadequately controlled with metformin alone, as compared to placebo plus metformin. Dapagliflozin is a novel, selective, sodium glucose co-transporter 2 (SGLT2) inhibitor.
The study also showed that individuals receiving dapagliflozin had statistically greater mean reductions in body weight compared to individuals taking placebo. Results from the 24-week study were presented at the 45th European Association for the Study of Diabetes Annual Meeting. This is the first public presentation of dapagliflozin Phase 3 data.
More interestingly, data on weight loss and blood pressure may be important adjuvants to glycemic control and is of great importance and hope in the days to come the SGLT2 inhibitors ( improved glycemic control) will play an important role in the type 2 diabetes. Given the continued rising prevalence of type 2 diabetes, there is an urgent need to have drugs of this kind..
Ref : http://www.astrazeneca.com/media/latest-press-releases/Dapagliflozen_Study014_EASD?itemId=7108139
Retinoic acid may provide relief for ulcerative colitis !
We know that Retinoic acid is the oxidized form of Vitamin A. It functions in determining position along embryonic anterior/posterior axis in chordates. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages. Retinoic acid acts by binding to heterodimers of the retinoic acid receptor (RAR) and the retinoid X receptor (RXR), which then bind to retinoic acid response elements (RAREs) in the regulatory regions of direct targets (including Hox genes), thereby activating gene transcription.Recently when I was reading a paper, found this interesting fact that is "retinoic acid, could be a beneficial treatment for people suffering from ulcerative colitis and other irritable bowel diseases. Specifically the researchers found that retinoic acid helps suppress out-of-control inflammation, which is a hallmark of active ulcerative colitis.
Pharmaceutical strategies based on this research may offer a promising alternative to the current approaches of managing immune diseases including, IBD, arthritis, multiple sclerosis, and so on, Aiping Bai, a researcher involved in the work from Nanchang University in Nanchang City, China claimed.
The studies ultimately found that treatment with retinoic acid reduced the inflammation in the colon by increasing the expression of FOXP3, a gene involved with immune system responses, as well as decreasing the expression of IL-17, a cytokine believed to cause inflammation. Because many experts believe that IL-17 directly relates to the uncontrolled inflammation seen in ulcerative colitis and irritable bowel disease, the discovery that retinoic acid reduces IL-17's ability to cause inflammation could accelerate the development of treatments for these chronic diseases.
Ref : http://www.jleukbio.org/cgi/content/abstract/86/4/959?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Aiping+Bai&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
RXi receives USPTO notices of allowance for certain siRNA sequence-specific patent applications..
In my earlier blog (January 25, 2009), titled "Diverse use of Nucleic acids....." I did mention about the RNA interference (RNAi) technology. Yes the dream has come true now "RXi Pharmaceuticals Corporation" has received Notices of Allowance from USPTO for small interfering RNA (siRNA) sequences targeting superoxide dismutase (SOD1), Amyloid beta (A4) precursor protein (APP), interleukin-1 receptor-associated kinase 4 (IRAK4), hepatocyte growth factor receptor (MET protooncogene) and cyclin-dependent kinase (cdk) inhibitor p27 (also known as MET protooncogene). Hope these class of compounds will get a boost and some new drugs from these class of compounds in the near future.....
More :
RXi receives USPTO notices of allowance for certain siRNA sequence-specific patent applications
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Saturday, October 3, 2009
NDA of Cladribine as a drug for Multiple Sclerosis !
When I was working with Innovasynth Technologies, Khopoli, I worked in the field of "antisense drugs" and as the company has tie up with many MNCs (working with these class of compounds) I had many times interacted with Serono, Pharmaceuticals (US) for some of the intermediates (oligonucleotides). When I read this article, I am happy there are many drugs still to be established as antisense drugs and more over this NDA (new drug application) is something to cherish.We know that 2-chlorodeoxyadenosine, Cladribine (Leustatin) is drug used to treat hairy cell leukemia (leukemic reticuloendotheliosis).
As a purine analog, it is a synthetic anticancer agent that also suppresses the immune system. Chemically, it mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, which interferes with the cell's ability to process DNA. It is easily destroyed by normal cells except for blood cells, with the result that it produces relatively few side effects and results in very little non-target cell loss.
Though it has been used to treat leukemic reticuloendotheliosis, other activities like B cell leukemias and lymphomas, such as mantle cell lymphoma are still to be established. Now EMD Serono has applied for this NDA with FDA. As per the claim by the company, Cladribine Tablets has the potential to be the first orally administered disease-modifying therapy available for people living with relapsing MS, as all disease-modifying therapies currently approved for the treatment of MS are parenteral therapies. Hope FDA will approve the drug and will help many patients with relapsing forms of multiple scleorosis will have a relief in the days to come..
Ref : http://www.emdserono.com/cmg.emdserono_us/en/images/Cladribine%20Tablets%20FDA%20Submission%20FINAL%20US%20FINAL_tcm115_44365.pdf
Friday, October 2, 2009
Herbicide as a catalyst to generate electricity from carbohydrates ?
In the recent times we have seen many research groups working on biofuels or alternative energy sources. This article is really interesting, here in the researchers (Brigham Young University) claim that with a help of a herbicide (they have'nt mentioned the name, but say a common herbicide which is cheap also) have developed a fuel cell – basically a battery with a gas tank – that harvests electricity from glucose and carbohydrates.
Deriving electrical energy from glucose and other carbohydrates under mild conditions is an important research objective because these biomolecules are abundant, renewable, have high energy density, and are convenient as fuels. The researchers Gerald Watt et.al., claim that viologen catalysts meet these demanding criteria by catalytically oxidizing glucose and other carbohydrates in a mildly alkaline solution, making possible a direct carbohydrate fuel cell. Formate and carbonate are major products of carbohydrate oxidation, demonstrating that extensive carbon–carbon bond breaking has occurred. A rudimentary fuel cell utilizing viologen catalysts and glucose or dihydroxyacetone as fuels demonstrated electrical power production at up to 20 mA/cm2 superficial current density. Improved catalyst function and cell design should significantly advance the efficiency and viability of direct carbohydrate fuel cell technology as a means of generating electrical energy from renewable biomass.
The effectiveness of this cheap and abundant herbicide is a boon to carbohydrate-based fuel cells. By contrast, hydrogen-based fuel cells like those developed by General Motors, require costly platinum as a catalyst. Congrats for this innovative idea....
Ref : http://byunews.byu.edu/archive09-Sep-sugar.aspx
Deriving electrical energy from glucose and other carbohydrates under mild conditions is an important research objective because these biomolecules are abundant, renewable, have high energy density, and are convenient as fuels. The researchers Gerald Watt et.al., claim that viologen catalysts meet these demanding criteria by catalytically oxidizing glucose and other carbohydrates in a mildly alkaline solution, making possible a direct carbohydrate fuel cell. Formate and carbonate are major products of carbohydrate oxidation, demonstrating that extensive carbon–carbon bond breaking has occurred. A rudimentary fuel cell utilizing viologen catalysts and glucose or dihydroxyacetone as fuels demonstrated electrical power production at up to 20 mA/cm2 superficial current density. Improved catalyst function and cell design should significantly advance the efficiency and viability of direct carbohydrate fuel cell technology as a means of generating electrical energy from renewable biomass.
The effectiveness of this cheap and abundant herbicide is a boon to carbohydrate-based fuel cells. By contrast, hydrogen-based fuel cells like those developed by General Motors, require costly platinum as a catalyst. Congrats for this innovative idea....
Ref : http://byunews.byu.edu/archive09-Sep-sugar.aspx
New markers for early detection Of type 1 diabetes !
As per the claim by the lead researchers Prof. Dr. Anette Ziegler and Dr. Peter Achenbach, genetic factors play a significant role in the development of type 1 diabetes. The scientists were able to show that specific variants of the zinc transporter gene SLC30A8 influence the risk for diabetes. The body needs this gene in order to produce ZnT8. This protein influences the zinc transport into the beta cells and plays a crucial role in their maturation and thus also in insulin secretion.
Beta cells of the islets of Langerhans in the pancreas secrete the vitally important insulin. Already prior to the onset of type 1 diabetes the body’s own immune system destroys the beta cells. If this destruction exceeds a certain threshold, the disease becomes manifest: The insulin deficiency leads to various metabolic disturbances, including elevated blood glucose levels. Autoantibodies to ZnT8 in combination with a specific variant of the zinc transporter gene were associated with an elevated diabetes risk. The researchers claims that "Autoantibodies to ZnT8 are an additional important marker for the progression of diabetes – especially in children who are already developing islet autoantibodies. Hence larger the number of different kinds of autoantibodies, the higher the risk for diabetes, and the younger the child with autoantibodies, the earlier disease onset will be. Its a good achievement. Congrats....
Ref : http://www.helmholtz-muenchen.de/en/press-and-media/press-releases/press-releases-2009/press-releases-2009-detail/article/12322/9/index.html
Ref : http://www.helmholtz-muenchen.de/en/press-and-media/press-releases/press-releases-2009/press-releases-2009-detail/article/12322/9/index.html
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