BCR-ABL-IN-6

BCR-ABL-IN-6 (9h) is a selective Bcr-Abl kinase inhibitor, with IC50s of 4.6 and 227 nM for Bcr-AblWTand A Bcr-AblT3151 respectively. BCR-ABL-IN-6 (9h) can inhibits Bcr-Abl kinase with strong affinity inside the cells, with an EC50 of 14.6 nM. BCR-ABL-IN-6 (9h) is an imatinib derivative which can be used for research of chronic myelogenous leukemia [1].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Bcr-Abl

IC50: 4.6 nM (Bcr-AblWT) and 227 nM (Bcr-AblT3151)[1].

BCR-ABL-IN-6 (9h) (10 μM; 1 h) againts with c-Src which is a closely related kinase domain of Bcr-Abl and exerts superior cellular potencies to imatinib[1]. .BCR-ABL-IN-6 (9h) (10 μM; 1 h) suppresses Bcr-Abl phosphorylation dose dependenly and results underscored selective antiproliferative effects towards Bcr-Abl [1]. BCR-ABL-IN-6 (9h) (10 μM; 1 h) shows great selectivity cytotoxic between K562 and L132 cell line[1]. BCR-ABL-IN-6 (9h) (10 μM) shows strong cytostatic activity against K562 and HL60(TB) cell lines[1]. BCR-ABL-IN-6 (9h) (10 μM) shows exceptional selective antiproliferative effects towards the Bcr-Abl positive leukemia cell K562[1]. Western Blot Analysis[1] Cell Line: K562 Concentration: 0.003, 0.01, 0.03, 0.1 and 0.3 μM Incubation Time: 1 h Result: Showed a dose-dependent suppression of Bcr-Abl phosphorylation. Cell Viability Assay[1] Cell Line: K562 and L132 cell lines Concentration: 10 μM Incubation Time: 1 h Result: Exerted cellular activity with GI50 less than 160 nM against the Bcr-Abl positive leukemia K562 cells and exerted superior cellular potencies to imatinib with GI50 of 0.02 μM. Showed selectivity cytotoxic effects to the normal cell L132 with GI50 of 9.27 μM. Cell Viability Assay Cell Line: K562 and HL60 cell lines Concentration: Incubation Time: Result: Strong cytostatic activity against K562 and HL60(TB) cell lines with GI values of 99.01% and 97.96%, respectively. Effects the Bcr-Abl positive leukemia cell K562 with GI50 less than 10 nM, more potent than imatinib.

BCR-ABL-IN-6 (9h) (5 mg/kg and 10 mg/kg; male ICR mice; for 9 h) takes 0.6 h to reach the maximum concentration (Cmax).With intravenous and oral administration, the AUClast values of BCR-ABL-IN-6 (9h) are 14018.7 ng h/mL and 174.7 ng h/mL. BCR-ABL-IN-6 (9h) intravenous administration is better,but unfavorable oral administration [1]. Animal Model: Male ICR mice[1] Dosage: 5 mg/kg and 10 mg/kg Administration: Intravenous and oral; 5 mg/kg and 10 mg/kg; for 9h Result: Oral administration is not as effective as intravenous injection, intravenous injection is better.

[1]. El-Damasy AK, et al. Design, synthesis, and biological evaluations of novel 3-amino-4-ethynyl indazole derivatives as Bcr-Abl kinase inhibitors with potent cellular antileukemic activity[J]. European Journal of Medicinal Chemistry, 2020, 207:112710.

[2]. El-Damasy AK, et al. Design, synthesis, and biological evaluations of novel 3-amino-4-ethynyl indazole derivatives as Bcr-Abl kinase inhibitors with potent cellular antileukemic activity[J]. European Journal of Medicinal Chemistry, 2020, 207:112710.