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CHMFL-ABL-053
本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。
CHMFL-ABL-053图片
CAS NO:1808287-83-3
包装与价格：
包装价格(元)
5mg电议
25mg电议

产品介绍
CHMFL-ABL-053 (Compound 18a) 是一种有效的、选择性的、可口服的 BCR-ABL、SRC 和 p38 激酶抑制剂，对 ABL1、SRC 和 p38 的 IC50 值分别为 70、90 和 62 nM。
Cas No.1808287-83-3
化学名2-((3-amino-4-methylphenyl)amino)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide
Canonical SMILESCC1=CC=C(NC2=NC(NC)=C(C(NC3=CC(NC(C4=CC=CC(C(F)(F)F)=C4)=O)=CC=C3C)=O)C=N2)C=C1N
分子式C28H26F3N7O2
分子量549.55
溶解度Soluble in DMSO
储存条件Store at -20°C
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping ConditionEvaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述

CHMFL-ABL-053 (compound 18a) is a BCR-ABL inhibitor with ABL1: IC50 of 70 nM. CHMFL-ABL-053 is derived from a dihydropyrimidopyrimidine core scaffold based compound 27 (GNF 7). [1]

CHMFL-ABL-053 inhibited the proliferation of CML cell lines K562 (GI50 = 14 nM), KU812 (GI50 = 25 nM) and MEG 01 (GI50 = 16 nM), through significant suppression of the BCR-ABL auto phosphorylation (EC50 = 100 nM) and downstream mediators such as STAT5, Crkl and ERK's phosphorylation. In the TEL fused isogenic BaF3 cells, CHMFL-ABL-053 exhibited strong binding ability against BLK, DDR1, DDR2, EPHA8, EphB6, HCK, LCK, p38α and SRC kinases. CHMFL-ABL-053 exhibited an IC50 of 70 nM against ABL1 kinase, inhibited p38α (IC50: 62 nM) and SRC kinase (IC50: 90 nM) by Invitrogen Select Screen biochemical assay. CHMFL-ABL-053 showed less potent to DDR1 (IC50: 292 nM) and DDR2 (IC50: 457 nM). CHMFL-ABL-053 did not exhibit apparent potency against c-KIT kinase (IC50: over 10000 nM). [1]

Pharmacokinetic study showed that CHMFL-ABL-053 had over 4 hours half-life and 24% bioavailability in rats. 50mg/kg/day dosage treatment could almost completely suppress the tumor progression in the K562 cells inoculated xenograft mouse model. As a potential useful drug candidate for CML, 18a is under extensive preclinical safety evaluation now. [1]

 

Reference:

1.Discovery of 2-((3-Amino-4-methylphenyl)amino)-N-(2-methyl-5-(3-(trifluoromethyl) benzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-ABL-053) as a Potent, Selective, and Orally Available BCR-ABL/SRC/p38 Kinase Inhibitor for Chronic Myeloid Leukemia.J Med Chem. 2016 Feb 5. [Epub ahead of print]