INHBE-3

INHBE-3 is a GalNAc-conjugated small interfering RNA (siRNA) designed to silence the *INHBE* gene, which encodes the hepatokine Activin E (Act E). Activin E is primarily expressed in the liver and is involved in the regulation of adipocyte lipolysis and adipose tissue remodeling. By reducing *INHBE* mRNA and circulating Activin E levels, INHBE-3 promotes a reduction in visceral fat mass, decreases adipocyte hypertrophy, and improves metabolic profiles without significantly impacting muscle mass. Developed by Wave Life Sciences, this compound serves as a preclinical precursor or related molecule to WVE-007, which is currently being evaluated in clinical trials for the treatment of obesity and overweight. Preclinical data in diet-induced obesity (DIO) mouse models have shown that INHBE-3 treatment leads to significant weight loss and adipose tissue remodeling, and can be combined with GLP-1 receptor agonists like semaglutide to enhance weight loss effects.