CHMFL-BMX-078_DataSheet_MedChemExpress

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Data Sheet

Product Name:Cat. No.:CAS No.:

Molecular Formula:Molecular Weight:Target:Pathway:Solubility:

CHMFL–BMX–078HY-1012671808288-51-8C33H35N7O6625.67BMX Kinase

Protein Tyrosine Kinase/RTKDMSO

BIOLOGICAL ACTIVITY: 

CHMFL–BMX–078 is a highly potent and selective type II irreversible BMX kinase inhibitor with an IC50 of 11 nM.IC50 & Target: IC50: 11 nM (BMX)[1]

In Vitro: Bone marrow kinase in the X chromosome (BMX, also called ETK) is a nonreceptor tyrosine kinase involved in

tumorigenicity, cell motility, adhesion, angiogenesis, proliferation, and differentiation. CHMFL–BMX–078 exhibits an IC50 of 11nM by formation of a covalent bond with cysteine 496 residue in the DFG–out inactive conformation of BMX. It displays a highselectivity profile against the 468 kinases/mutants in the KINOMEscan evaluation and achieves at least 40–fold selectivity overBTK kinase (IC50=437 nM). For inactive state of BMX kinase, CHMFL–BMX–078 displays a binding Kd of 81 nM, while for the activestate of BMX kinase, it exhibits a binding Kd of 10200 nM. CHMFL–BMX–078 exhibits antiproliferative effects against

BaF3–TEL–BMX cells (GI50=0.016 μM) and selectivity over parental BaF3 cells. CHMFL–BMX–078 is about 80–fold more potentagainst BMX wt (EC50=5.8 nM) than C496S mutant (EC50=459 nM) for the inhibition of BMX total tyrosine phosphorylation.CHMFL–BMX–078 would serve as a useful pharmacological tool to elucidate the detailed mechanism of BMX mediated signalingpathways[1].

In Vivo: CHMFL–BMX–078 exhibits a short half–life (T1/2=0.80 h) in iv injection. CHMFL–BMX–078 also displays an acceptable Cmax

(13565.23 ng/mL) and AUC0–t (1386.41 ng/mL h) in iv injection. However, it is not absorbed by oral administration, indicating thatthis compound could be administrated through iv or ip injection when used as a research tool[1].

PROTOCOL (Extracted from published papers and Only for reference)

Kinase Assay:[1]The kinase reaction system contains BMX or BTK, 1 μL of serially diluted CHMFL–BMX–078, and substrate Polypeptidewith 100 μM ATP. The reaction in each tube is started immediately by adding ATP and kept going for an hour under 37 °C.After the tube cooled for 5 min at room temperature, 5 μL solvent reactions are carried out in a 384–well plate. Then 5 μL ofADP–Glo reagent is added into each well to stop the reaction and consume the remaining ATP within 40 min. At the end, 10 μL ofkinase detection reagent is added into the well and incubated for 30 min to produce a luminescence signal. Luminescence signal ismeasured with an automated plate reader[1].

Animal Administration: CHMFL–BMX–078 is dissolved in 55% saline containing 5% DMSO and 40% PEG400 by vortex. The finalconcentration of the stock solution is 1 mg/mL for administration. [1]Rat: Six 8–week–old male Sprague-Dawley rats are fastedovernight before starting drug treatment via intravenous and oral administration. Animal blood collection time points are asfollows. For groups 1, 3, and 5 (intravenous): 1 min, 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, and 8 h before and after administrationis selected. For group 2, 4, and 6 (oral): 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, and 24 h before and after dosing. The plasma iscollected for analysis[1].

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References:

[1]. Liang X, et al. Discovery of

2–((3–Acrylamido–4–methylphenyl)amino)–N–(2–methyl–5–(3,4,5–trimethoxybenzamido)phenyl)–4–(methylamino)pyrimidine–5–carboxamide

(CHMFL–BMX–078) as a Highly Potent and Selective Type II Irreversible Bone Marrow Kinase in the X Chromosome (BMX) Kinase Inhibitor. J Med Chem. 2017Mar 9;60(5):1793–1816.

Caution: Product has not been fully validated for medical applications. For research use only.

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