IHMT-15130 is a potent, selective and irreversible BMX kinase inhibitor with IC50 of 1.47 nM, covalently targets Cys496 of BMX.
IHMT-15130 displayed selectivity over CSK kinase (IC50 > 25,000 nM), compare with BTK/BMX dual inhibitor Ibrutinib.
IHMT-15130 achieved 10-fold selectivity of BMX over BTK kinase.
IHMT-15130 has IC50 of 1.8 nM for engineered BaF3 cells stably expressing TEL-fused BMX kinase (BaF3-TEL-BMX).
IHMT-15130 dose-dependently inhibits the phosphorylation of BMX with EC50 of 3.4 nM in Western blotting using BaF3-TEL-BMX cells lines.
IHMT-15130 binds to the Cys496 of BMX in the ATP binding site, exhibits potent binding affinity to BMX kinase with Ki of 24.5 nM.
dose-dependently reduces LPS-activated phosphorylation levels of BMX, also suppresses BMX-induced tyrosine phosphorylation of STAT3, p38, JNK, and NF-κB in RAW264.7 cells.
IHMT-15130 dose-dependently suppresses the secretion of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α in both human PBMC and murine BMDM cells.
IHMT-15130 dose-dependently inhibits the phosphorylation of BMX kinase and its downstream MAPK, AKT, S6K, and RPS6 signals.
IHMT-15130 effectively reduced the secretion of inflammatory cytokines, alleviated angiotensin II (Ang II)-induced myocardial hypertrophy in a murine model.