XMU-MP-3 is a robust, non-covalent inhibitor of BTK, exhibiting exceptional potency with IC50 values of 10.7 nM and 17.0 nM for BTK WT and BTK C481S mutation, respectively, in the presence of 10 μM ATP. Moreover, XMU-MP-3 elicits apoptosis.

BTK (C481S):17.0 nM (IC50), BTK (WT):10.7 nM (IC50)

XMU-MP-3 (0.001-10000 nM; 48 hours) inhibits BTK-transformed Ba/F3 cell proliferation with an IC 50 of 11.4 nM[1]. XMU-MP-3 (1-10000 nM) inhibits the proliferation of JeKo-1, Ramos and NALM-6 with IC 50 values of 326.6 nM, 685.6 nM and 1065 nM, respectively[1]. XMU-MP-3 (0.001-10000 nM) maintains inhibitory potency with an IC 50 of 182.3 nM against BTK(C481S)-Ba/F3 cells[1]. XMU-MP-3 (5000 nM) induces apoptosis in BTK (C481S) Ba/F3 cells[1]. XMU-MP-3 (10-1000 nM; 4 hours) inhibits both the auto- and trans-phosphorylation of BTK at the site of Y223 and Y551 in a dose-dependent manner in BTK-transformed Ba/F3 cells[1]. Cell Proliferation Assay[1]Cell Line: BTK-transformed and parental Ba/F3 cells Concentration: 0.001, 0.01, 0.1, 1, 10, 100, 1000, 10000 nM Incubation Time: 48 hours Result: Inhibited BTK-transformed Ba/F3 cell proliferation with an IC 50 of 11.4 nM, while it showed negligible anti-proliferative effects on parental wild-type Ba/F3 cells (IC 50 >10000 nM). Western Blot Analysis[1]Cell Line: BTK-transformed Ba/F3 cells Concentration: 10, 50, 100, 500, 1000 nM Incubation Time: 4 hours Result: The phosphorylation levels of BTK Y223 and Y551 were reduced significantly at concentrations as low as 100 nM, and completely suppressed at the concentration of 1000 nM.

XMU-MP-3 (25 and 50 mg/kg) substantially suppresses tumor growth in mouse xenograft models[1]. Animal Model: Nu/nu BALB/c mice (4-6 weeks of age) bearing BTK-transformed Ba/F3 and Ramos xenograft models[1]Dosage: 25 and 50 mg/kg Administration: Treated by tail vein injection; the injection volume was 0.1 mL per 10 g; daily for 14 days Result: Significantly reduced the tumor size without affecting animal weights.