XMU-MP-3

XMU-MP-3 is a potent non-covalent BTK inhibitor with IC50s of 10.7 nM and 17.0 nM for BTK WT and BTK C481S mutation in the presence of 10 μM ATP, respectively. XMU-MP-3 also induces apoptosis[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Btk

IC50: 10.7 nM (BTK WT), 17.0 nM (BTK C481S), Apoptosis[1]

XMU-MP-3 (0.001-10000 nM; 48 hours) inhibits BTK-transformed Ba/F3 cell proliferation with an IC50 of 11.4 nM[1]. XMU-MP-3 (1-10000 nM) inhibits the proliferation of JeKo-1, Ramos and NALM-6 with IC50 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 IC50 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 IC50 of 11.4 nM, while it showed negligible anti-proliferative effects on parental wild-type Ba/F3 cells (IC50 >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.

[1]. Fu Gui, et al. A Non-Covalent Inhibitor XMU-MP-3 Overrides Ibrutinib-Resistant Btk C481S Mutation in B-cell Malignancies. Br J Pharmacol. 2019 Dec;176(23):4491-4509.