AMG131

AMG131 (INT131), a potent and highly selective PPARγ partial agonist, binds to PPARγ and displaces Rosiglitazone with a Ki of ~10 nM. AMG131 can be used for research of type-2 diabetes mellitus (T2DM)[1][2].

Signaling Pathways >> Cell Cycle/DNA Damage >> PPAR

Research Areas >> Metabolic Disease

PPARγ

AMG131 (INT131) binds to PPARγ and displaces Rosiglitazone with a Ki of ~10 nM, demonstrating ~20-fold higher affinity than either Rosiglitazone or Pioglitazone, and with greater than 1000-fold selectivity for PPARγ over PPARα, PPARδ, or a set of other nuclear receptors. AMG131 is highly selective for PPARγ, with no binding to PPARα or δ at 10 μM, 1000 fold over the Ki for PPARγ[1].

AMG131 (INT131; 80 mg/kg; 14-day oral treatment) increases in glucose tolerance in Zucker (fa/fa) rats following[2] Animal Model: Male Zucker fatty (fa/fa) rats ages 7-8 weeks[2] Dosage: 80 mg/kg Administration: Administered once daily by oral gavage for 14 days Result: Exhibited maximal efficacy comparable to that of Rosiglitazone with respect to plasma glucose clearance in an oral glucose tolerance test. Reduced baseline insulin levels, similar to Rosiglitazone, could improve insulin sensitivity in treated animals.

[1]. Linda S Higgins,et al. The Development of INT131 as a Selective PPARgamma Modulator: Approach to a Safer Insulin Sensitizer. PPAR Res. 2008;2008:936906.

[2]. Alykhan Motani, et al. INT131: a selective modulator of PPAR gamma. J Mol Biol. 2009 Mar 13;386(5):1301-11.