Highly selective peroxisome proliferator-activated receptor δ (PPARδ) modulator demonstrates improved safety profile compared to GW501516

Bharat Lagu; Arthur F Kluge; Matthew M Goddeeris; Effie Tozzo; Ross A Fredenburg; Shekar Chellur; Ramesh S Senaiar; Mahaboobi Jaleel; D Ravi Krishna Babu; Nirbhay K Tiwari; Taisuke Takahashi; Michael A Patane

doi:10.1016/j.bmcl.2017.11.006

Highly selective peroxisome proliferator-activated receptor δ (PPARδ) modulator demonstrates improved safety profile compared to GW501516

Bioorg Med Chem Lett. 2018 Feb 1;28(3):533-536. doi: 10.1016/j.bmcl.2017.11.006. Epub 2017 Nov 4.

Affiliations

¹ Mitobridge, Inc., 1030 Massachusetts Ave., Cambridge, MA 02138, United States. Electronic address: blagu@mitobridge.com.
² Mitobridge, Inc., 1030 Massachusetts Ave., Cambridge, MA 02138, United States.
³ Aurigene Discovery Technologies, Ltd., Bengaluru, Karnataka, India.
⁴ Astellas Pharma, Tsukuba, Japan.

PMID: 29275935
DOI: 10.1016/j.bmcl.2017.11.006

Abstract

Compound 1 regulates significantly fewer genes than the PPARδ modulator, GW501516. Both compounds are efficacious in a thermal injury model of muscle regeneration. The restricted gene profile of 1 relative to GW501516 suggests that 1 may be pharmacoequivalent to GW501516 with fewer PPAR-related safety concerns.

Keywords: GW501516; Gene expression; Ki-67; PPARδ modulator; Thermal injury model.

MeSH terms

Animals
Cell Proliferation / drug effects
Disease Models, Animal
Dose-Response Relationship, Drug
Humans
Mice
Molecular Structure
PPAR delta / metabolism*
Rats
Structure-Activity Relationship
Thiazoles / pharmacology*

Substances

GW 501516
PPAR delta
Thiazoles