Optimized chemical probes for REV-ERBα.

Basic Information

ID: ALA2380244

Journal: J Med Chem

Title: Optimized chemical probes for REV-ERBα.

Authors: Trump RP, Bresciani S, Cooper AW, Tellam JP, Wojno J, Blaikley J, Orband-Miller LA, Kashatus JA, Boudjelal M, Dawson HC, Loudon A, Ray D, Grant D, Farrow SN, Willson TM, Tomkinson NC.

Abstract: REV-ERBα has emerged as an important target for regulation of circadian rhythm and its associated physiology. Herein, we report on the optimization of a series of REV-ERBα agonists based on GSK4112 (1) for potency, selectivity, and bioavailability. (1) Potent REV-ERBα agonists 4, 10, 16, and 23 are detailed for their ability to suppress BMAL and IL-6 expression from human cells while also demonstrating excellent selectivity over LXRα. Amine 4 demonstrated in vivo bioavailability after either iv or oral dosing.

CiteXplore: 23656296

DOI: 10.1021/jm400458q

Patent ID: