Main Category: Diabetes
Also Included In: Obesity / Weight Loss / Fitness
Article Date: 06 Sep 2011 ? 1:00 PDT
email to a friend ? printer friendly ? opinions ?
<!? rate article
Patient / Public:
Healthcare Prof:4 (1 votes)
In a joint study, scientists from The Scripps Research Institute and Harvard University?s Dana-Farber Cancer Institute have established a new class of anti-diabetic compound that targets a unique molecular switch.
The finding paves the way for the development of anti-diabetic therapeutics with minimal adverse side effects plaguing currently available drugs such as Avandia (rosiglitazone), scheduled to be removed from pharmacy shelves this fall due to concerns about increased risk of heart attack.
The new study, led by Patrick R. Griffin, professor and chair of the Department of Molecular Therapeutics at Scripps Florida, Bruce Spiegelman, professor of cell biology at the Dana-Farber Cancer Institute, and Theodore Kamenecka, associate scientific director of medicinal chemistry at Scripps Florida, was published September 4, 2011, in the journal Nature. The study describes a new compound known as SR1664.
?In this study, we demonstrate that we have discovered novel compounds that work effectively through a unique mechanism of action on a well-validated clinical target for diabetes,? said Griffin. ?This unique mechanism of action appears to significantly limit side effects associated with marketed drugs. This study is a great example of interdisciplinary, inter-institutional collaboration with chemistry, biochemistry, structural biology, and pharmacology.?
?It appears that we may have an opportunity to develop entire new classes of drugs for diabetes and perhaps other metabolic disorders,? said Spiegelman.
Diabetes affects nearly 24 million children and adults in the United States, according to the America Diabetes Association.
A Viable Therapeutic Target
The study follows previous research by the authors published last year in Nature (Volume 466, Issue 7305, 451-456) that suggested an obesity-linked mechanism that may be involved in the development of insulin-resistance. In that research, the team found disruptions in various genes when a protein known as PPAR? undergoes phosphorylation (when a phosphate group is added to a protein) by the kinase Cdk5, an enzyme involved in a number of important sensory pathways.
The new study confirms that blockage of Cdk5?s action on PPARG is a viable therapeutic approach for development of anti-diabetic agents. The new SR1664 compound is a potent binder to the nuclear receptor PPARG, but does not activate gene transcription via the receptor?s normal mechanism.
While Griffin stressed the difficulty of fully assessing side effects of new compounds such as SR1664, the new research is extremely positive in that it clearly demonstrated fewer of the major well-documented side effects, such as weight gain or increased plasma volume, from SR1664 as compared to Avandia in diabetic mice.
While both the mice treated with Avandia and those treated with SR1664 demonstrated improved blood sugar levels, those treated with Avandia showed weight gain and increased fluid retention within a few days of beginning treatment; those being treated with SR1664 showed none of these side effects. In cell culture studies, SR1664 also appeared to have little effect on bone formation, nor did it increase fat generation in bone cells, another side effect of current therapies such as Avandia.
While S1664 likely will not be developed as a drug, it now serves as a molecular scaffolding for the creation of similar compounds with potential to treat diabetes. ?With data in hand showing that our compounds are as efficacious as the currently marketed PPARG modulators, while demonstrating a significant improvement of side effects in limited studies, we are now advancing newer compounds with improved pharmaceutical properties into additional studies,? Griffin said.
The first authors, denoted as equal contributors to this study, ?Anti-Diabetic Actions of a Non-Agonist PPARG Ligand Blocking Cdk5-Mediated Phosphorylation,? are Jang Hyun Choi and Alexander S. Banks of Dana-Farber Cancer Institute and Theodore M. Kamenecka and Scott A. Busby of The Scripps Research Institute. Other authors include Michael J. Chalmers, Naresh Kumar, Dana S. Kuruvilla, Youseung Shin, Yuanjun He, David Marciano, and Michael D. Cameron of Scripps Research; Dina Laznik of the Dana-Farber Cancer Institute; Michael J. Jurczak and Gerald I. Shulman of the Howard Hughes Medical Institute; Stephan C. Sch?rer and Du?ica Vidovi? of the University of Miami; and John B. Bruning of Texas AM University.
The study was supported by The National Institutes of Health.
- Additional
- References
- Citations
Article adapted by Medical News Today from original press release.
Visit our ?diabetes section for the latest news on this subject.
Please use one of the following formats to cite this article in your essay, paper or report:
APA
Mika Ono (2011, September 6). New Class Of Anti-Diabetic Compound Established By Scripps Research Scientists. Medical News Today. Retrieved September 6, 2011 from http://www.medicalnewstoday.com/releases/233876.php
MLA
Mika Ono. ?New Class Of Anti-Diabetic Compound Established By Scripps Research Scientists?. Medical News Today, September 6, 2011. Web. 6 Sep, 2011.
Please note: If no author information is provided, the source is cited instead.
Please note that we publish your name, but we do not publish your email address. It is only used to let
you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.
If you write about specific medications or operations, please do not name health care professionals by name.
All opinions are moderated before being included (to stop spam)
Contact Our News Editors
For any corrections of factual information, or to contact the editors please use our feedback form.
Please send any medical news or health news press releases to:
Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care
professional. For more information, please read our terms and conditions.
Privacy Policy |
Terms and Conditions
MediLexicon International Ltd
Bexhill-on-Sea, United Kingdom
MediLexicon International Ltd ? 2004-2011 All rights reserved.
Article source: http://www.medicalnewstoday.com/releases/233876.php
hawaii five o doe sirius kreayshawn tyler the creator us open tennis us open tennis
কোন মন্তব্য নেই:
একটি মন্তব্য পোস্ট করুন