5.05021

BMX-IN-1

• Synonym(s): BMX-IN-1, 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 Inhibi
• Empirical Formula (Hill Notation): C₂₉H₂₄N₄O₄S
• CAS Number: 1431525-23-3
• Molecular Weight: 524.59
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Assay: ≥95% (HPLC)
• Quality Level: 100
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: off-white
• solubility: DMSO: 12.5 mg/mL
• storage temp.: −20°C
• InChI: 1S/C29H24N4O4S/c1-4-27(34)31-26-16-23(12-5-18(26)2)33-28(35)14-9-21-17-30-25-13-8-20(15-24(25)29(21)33)19-6-10-22(11-7-19)32-38(3,36)37/h4-17,32H,1H2,2-3H3,(H,31,34)
• InChI key: SFMJNHNUOVADRW-UHFFFAOYSA-N

Description

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 (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).

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).

Biochem/physiol Actions

Cell permeable: yes

Primary Target
BMX

Reversible: no

Secondary Target
BTK

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

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.

Other Notes

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

Legal Information

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

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable