GW4869

GW4869 is a **cell-permeable, noncompetitive inhibitor** of **neutral sphingomyelinase 2 (nSMase2/SMPD2)**, with an IC50 of approximately 1 µM[1][5][9]. By inhibiting nSMase2, GW4869 **prevents the hydrolysis of sphingomyelin to ceramide**, thereby suppressing ceramide-driven inward budding of multivesicular bodies and **blocking the biogenesis and release of exosomes**[1][5][7][9]. This action also suppresses the secretion of pro-inflammatory cytokines (such as TNF-alpha, IL-1β, and IL-6), impairs exosome-mediated intercellular communication, and has been shown to **attenuate inflammatory responses and cell death** in various cellular and animal models[1][2][5]. GW4869 has been studied in the context of **cancer (especially resistance mechanisms and EMT in NSCLC), sepsis, neurodegenerative diseases (AD, PD), and stroke models**[4][5][6]. It is primarily used as a **research tool**, not a therapeutic drug[1][9]. The originator is GlaxoSmithKline[9].

Other names

CHEBI:231549N,N′-Bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-3,3′-p-phenylene-bis-acrylamide dihydrochloride