The Development of INT131 as a Selective PPARγ Modulator: Approach to a Safer Insulin Sensitizer
Citation
Higgins, Linda S. and Christos S. Mantzoros. 2008. The Development of INT131 as a Selective PPARγ Modulator: Approach to a Safer Insulin Sensitizer. PPAR Research 2008: 936906.Abstract
INT131 (formerly T0903131, T131, AMG131) is a potentnon-thiazolidinedione (TZD) selective peroxisome proliferator-activated receptor
γ modulator (SPPARM) currently in Phase 2 clinical trials for treatment of type-2 diabetes mellitus (T2DM). This new chemical entity represents a second generation SPPARM approach developed after the first generation
PPARγ full agonists to address their inherent limitations. INT131 was specifically and carefully designed using preclinical models to exhibit a biological profile of strong efficacy with
de minimis side effects compared to PPARγ full agonists. As a potent PPARγ modulator, INT131 binds to PPARγ with high affinity. In pharmacology models of diabetes and in early clinical studies, it achieved a high level of efficacy in terms of antidiabetic actions such as insulin sensitization and glucose and insulin lowering, but had little activity in terms of other, undesired, effects associated with TZD PPARγ full agonists such as edema and adipogenesis. Ongoing clinical development is directed at translating these findings into establishing a novel and effective treatment for T2DM patients with an improved safety profile in relation to that currently available.
Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2522386/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:4891675
Collections
- HMS Scholarly Articles [17922]
- SPH Scholarly Articles [6362]
Contact administrator regarding this item (to report mistakes or request changes)