NX-2127 (C09-1156-653)

NX-2127 is an orally and potent BTK inhibitor, inducing degradation of the mutated BTK C481S in cells. NX-2127 inhibits proliferation of BTK C481S mutant TMD8 cells, more effectively than Ibrutinib ( HY-10997 ). NX-2127 catalyzes the degradation of Ikaros (IKZF1) and Aiolos (IKZF3) with of 25 nM and 54 nM, respectively. NX-2127 stimulates T cell activation and increases IL-2 production in primary human T Cells.In VitroNX-2127 inhibits proliferation of BTK-C481S mutant TMD8 cells with an EC 50 value <30 nM. NX-2127 increases IL-2 production in primary human T Cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoNX-2127 (1 mg/kg; po; once daily for 14 days) demonstrates potent degradation of BTK in cynomolgus monkeys in vivo . NX-2127 (po) leads to dose-proportional exposure in plasma and BTK degradation to <10% of baseline levels in circulating and splenic B cells . NX-2127 results in superior tumor growth inhibition (TGI) in both WT TMD8 and C481S mutant xenograft models in mouse . MCE has not independently confirmed the accuracy of these methods. They are for reference only.Form:Solid. Specification: 0.98 Molecular Formula: C39H45N9O5 Molecular Weight: 719.83