Delving into the Latest Updates on SHM-115 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target-

Mechanism-

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication

Obesity

Inactive Indication-

Originator Organization

University of Virginia

The University of New South Wales

Active Organization

The University of New South Wales

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Small-molecule mitochondrial uncouplers are gaining recognition as potential therapeutics for metabolic diseases such as obesity, diabetes, and nonalcoholic steatohepatitis (NASH). Specifically, heterocycles derived from BAM15, a potent and mitochondria-selective uncoupler, have yielded promising preclinical candidates that are efficacious in animal models of obesity and NASH. In this study, we report the structure-activity relationship studies of 6-amino-[1,2,5]oxadiazolo[3,4-b]pyridin-5-ol derivatives. Using oxygen consumption rate as a readout of mitochondrial uncoupling, we established 5-hydroxyoxadiazolopyridines as mild uncouplers. In particular, SHM115, which contains a pentafluoro aniline, had an EC₅₀ value of 17 μM and exhibited 75% oral bioavailability. SHM115 treatment increased the energy expenditure and lowered the body fat mass in two diet-induced obesity mouse models, including an obesity prevention model and an obesity reversal model. Taken together, our findings demonstrate the therapeutic potential of mild mitochondrial uncouplers for the prevention of diet-induced obesity.

100 Deals associated with SHM-115

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