SR2067 Reveals a Unique Kinetic and Structural Signature for PPARγ Partial Agonism.

ABSTRACT: Synthetic full agonists of PPARγ have been prescribed for the treatment of diabetes due to their ability to regulate glucose homeostasis and insulin sensitization. While the use of full agonists of PPARγ has been hampered due to severe side effects, partial agonists have shown promise due to their decreased incidence of such side effects in preclinical models. No kinetic information has been forthcoming in regard to the mechanism of full versus partial agonism of PPARγ to date. Here, we describe the discovery of a partial agonist, SR2067. A co-crystal structure obtained at 2.2 Å resolution demonstrates that interactions with the β-sheet are driven exclusively via hydrophobic interactions mediated through a naphthalene group, an observation that is unique from other partial agonists. Surfac

SUBMITTER: van Marrewijk LM 

PROVIDER: S-EPMC4819005 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature