U73122

U73122 is a synthetic small-molecule aza-steroid widely used as a research tool compound and originally characterized as a selective inhibitor of phosphoinositide-specific phospholipase C (PLC), with reported IC50 values around 1–6 µM for PLC-β3 in cell-based systems.[1][2][3][13] It contains an electrophilic maleimide moiety on a 3‑methoxyestradiol core, enabling covalent reaction with cellular nucleophiles and leading to inhibition of PLC-dependent phosphatidylinositol 4,5-bisphosphate hydrolysis, subsequent inositol 1,4,5-trisphosphate and diacylglycerol generation, and downstream Ca2+ and protein kinase C signaling.[1][2][3][6][7][9][13] Subsequent work has shown that U73122 also inhibits phospholipase A2, the sarcoplasmic reticulum Ca2+ pump, and human 5‑lipoxygenase, and exerts diverse effects including antiplatelet activity, inhibition of neutrophil adhesion and degranulation, modulation of Ca2+ homeostasis, and antinociceptive actions, indicating that it is a relatively nonselective covalent modulator of multiple signaling pathways rather than a strictly specific PLC inhibitor.[1][3][4][5][7][9][13]

Other names

1-[6-[[(17β)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione1-[6-[[(8R,9S,13S,14S,17S)-3-methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]amino]hexyl]pyrrole-2,5-dione3-O-methyl-17β-estradiol 17-(6-maleimidylhexyl)amine derivative