GS-1427

GS-1427 is an investigational, orally bioavailable small molecule prodrug developed by Gilead Sciences for the treatment of inflammatory bowel diseases, including ulcerative colitis and Crohn's disease. It is designed to be converted in vivo into its active metabolite, GS-4875, which serves as a potent and selective inhibitor of Tumor Progression Locus 2 (TPL2), also known as Mitogen-Activated Protein Kinase Kinase Kinase 8 (MAP3K8). TPL2 is a key signaling kinase that integrates signals from various inflammatory stimuli, such as toll-like receptors and TNF-α, to regulate the production of pro-inflammatory cytokines like TNF-α, IL-1β, and IL-6 via the MEK/ERK pathway. By inhibiting TPL2, GS-1427 aims to modulate the inflammatory response and provide therapeutic benefit in patients with moderate-to-severe ulcerative colitis. Clinical development reached Phase 2, although recent pipeline updates indicate the program has been terminated.

Other names

(phosphonooxy)methyln-[(s)-[1-(bicyclo[1.1.1]pentan1-yl)-1h-1,2,3-triazol-4-yl](2-methyl-1-oxo-1,2-dihydroisoquinolin-5-yl)methyl]-n-{8-chloro-3-cyano-4-[(2,2-dimethylpropyl)amino]quinolin-6-yl]carbamateGS-4875 prodrugGS4875 prodrugGS 4875 prodrug