Biochem/physiol Actions

Reversible: no

Secondary TargetBTK

Primary TargetBMX

Cell permeable: yes

General description

A cell-permeable tricyclic quinoline-acrylamide compound that potently inhibits BMX and BTK kinase activity (IC₅₀ = 8 and 10.4 nM, 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 653 nM, respectively). Only PI 3-Kγ/PIK3CG, SBK1, PIP5K2C (by ≥94% at 1 µM), and TXK (by 75% at 1 µM) 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 = 25 nM), while being much less effective against TEL-BLK, TEL-JAK1, TEL-JAK2, TEL-JAK3, or TEL-TYK2E957D transformed Ba/F3 (GI₅₀ = ≥3.64 µM) or a panel of 5 prostate cancer cell lines (GI₅₀ ≥2.46 µM).

A cell-permeable tricyclic quinoline-acrylamide compound that potently inhibits BMX and BTK kinase activity (IC₅₀ = 8 and 10.4 nM, respectively) by covalently targeting ATP-binding site cysteine (Ser496 and S481 of respective human sequence), while being less potent against 3 other TEC family kinases with the same conserved cysteine (IC₅₀ = 175, 377, and 653 nM against TEC, JAK3, and BLK, respectively) and completely ineffective toward BMX C496S even at concentrations as high as 10 µM. Only PI 3-Kγ/PIK3CG, SBK1, and PIP5K2C are significantly inhibited by BMX-IN-1 (by ≥94% at 1 µM) in a selectivity profiling against 437 other kinase constructs, including TEC family members EGFR/T790M, ITK (IC₅₀ = 4.28 and 5.25 µM, respectively), TXK, ErbB2/Her2, ErbB4/Her4, JAK1, and JAK2 (75%, 10%, 22%, 13%, and 14% inhibition at 1 µM, respectively). Potently inhibits the proliferation of TEL-BMX transformed Ba/F3 Ba/F3 (GI₅₀ = 25 nM), while being much less effective against TEL-BLK, TEL-JAK1, TEL-JAK2, TEL-JAK3, or TEL-TYK2E957D transformed Ba/F3 (GI₅₀ = 3.64, 4.92, 5.83, 7.98, and 6.09 µM, respectively) or prostate cancer cells using a panel of 5 established lines (GI₅₀ ≥2.46 µM).

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Liu, F., et al. 2013. ACS Chem. Biol.8, 1423.

Packaging

Packaged under inert gas

10 mg in Glass bottle

Reconstitution

Following reconstitution, aliquot and freeze (-70°C). Stock solutions are stable for up to 3 months at -70°C.

Use only fresh DMSO for reconstitution.

Warning

Toxicity: Standard Handling (A)