PSTC1411

PSTC1411 is a novel, orally bioavailable G-protein-biased agonist of the apelin receptor (APJ) being developed for the treatment of obesity. Unlike non-biased agonists, PSTC1411 selectively activates the cAMP/G-protein signaling pathway with reduced β-arrestin recruitment, a profile intended to optimize metabolic benefits while minimizing potential receptor desensitization. Preclinical studies in diet-induced obesity (DIO) mice have shown that PSTC1411 as a monotherapy induces significant dose-dependent weight loss (up to 22%) and acts synergistically with GLP-1 receptor agonists (GLP-1RAs) such as semaglutide and orforglipron. A key differentiator for PSTC1411 is its ability to promote muscle-sparing weight loss, increase muscle fiber area, and improve muscle function, addressing a common limitation of current incretin-based therapies. The drug also appears to reduce food intake and increase energy expenditure.