A cell-permeable tricyclic quinoline-acrylamide compound that potently inhibits BMX and BTK kinase activity (IC50 = 8 and 10.4nM, respectively) by covalently targeting ATP-binding site cysteine, while being less potent against TEC family kinases TEC, JAK3, BLK with the same conserved cysteine (IC50 = 175, 377, and 653nM, respectively). Only PI 3-K gamma/PIK3CG, SBK1, PIP5K2C (by ≥94% at 1uM), and TXK (by 75% at 1uM) are significantly inhibited by BMX-IN-1 in a selectivity profiling against 437 other kinase constructs. Potently inhibits the proliferation of TEL-BMX transformed Ba/F3 Ba/F3 (GI50 = 25nM), while being much less effective against TEL-BLK, TEL-JAK1, TEL-JAK2, TEL-JAK3, or TEL-TYK2E957D transformed Ba/F3 (GI50 = ≥3.64uM) or a panel of 5 prostate cancer cell lines (GI50 ≥2.46uM).
Synonyms: N-(2-Methyl-5-(9-(4-(methylsulfonamido)phenyl)-2-oxobenzo[h][1,6]naphthyridin-1(2H)-yl)phenyl)acrylamide, BMX/BTK Inhibitor, Bruton's Tyrosine Kinase Inhibitor IV, BLK Inhibitor I, BMX Inhibitor I, JAK3 Inhibitor XIII, PI 3-K Inhibitor XX, PIP5K2C Inhibitor I, SBK1 Inhibitor I, TEC Inhibitor I, TXK Inhibitor I
Primary Target:BMX
Secondary Target:BTK
Solubility:DMSO
Molecular Formula:C₂₉H₂₄N₄O₄S
Appearance:Supplied as an off-white solid.
Purity:≥95% (HPLC)
Packaging:Under inert gas
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 12 months after receipt at -20°C. Reconstitute with sterile buffer or ddH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
