CHMFL-ABL-053

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). 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). 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.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]

Product information

CAS Number: 1808287-83-3

Molecular Weight: 549.55

Formula: C28H26F3N7O2

Chemical Name: 2-[(3-amino-4-methylphenyl)amino]-N-{2-methyl-5-[3-(trifluoromethyl)benzamido]phenyl}-4-(methylamino)pyrimidine-5-carboxamide

Smiles: CNC1N=C(NC2C=C(N)C(C)=CC=2)N=CC=1C(=O)NC1=CC(=CC=C1C)NC(=O)C1C=C(C=CC=1)C(F)(F)F

InChiKey: GXMFPDCIAWSZFR-UHFFFAOYSA-N

InChi: InChI=1S/C28H26F3N7O2/c1-15-7-9-19(12-22(15)32)36-27-34-14-21(24(33-3)38-27)26(40)37-23-13-20(10-8-16(23)2)35-25(39)17-5-4-6-18(11-17)28(29,30)31/h4-14H,32H2,1-3H3,(H,35,39)(H,37,40)(H2,33,34,36,38)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

Products are for research use only. Not for human use.