CHMFL-ABL-053

• CAT Number: I006109
• CAS Number: 1808287-83-3
• Molecular Formula: C28H26F3N7O2
• Molecular Weight: 549.558
• Purity: ≥95%
• Synonyms: CHMFL-ABL-053; CHMFL-ABL053; CHMFL-ABL 053.;2‑((3-Amino-4-methylphenyl)amino)‑N‑(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide
• Target: BCR-ABL/SRC/p38 kinase inhibitor
• Solubility: Soluble in DMSO, not in water
• Storage: 0 - 4°C for short term ,or -20 °C for long term
• IUPAC Name: 2-(3-amino-4-methylanilino)-4-(methylamino)-N-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]pyrimidine-5-carboxamide
• 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)
• InChIKey: GXMFPDCIAWSZFR-UHFFFAOYSA-N
• SMILES: CC1=C(C=C(C=C1)NC2=NC=C(C(=N2)NC)C(=O)NC3=C(C=CC(=C3)NC(=O)C4=CC(=CC=C4)C(F)(F)F)C)N

CHMFL-ABL-053 is a potent, selective and orally available BCR-ABL/SRC/p38 kinase inhibitor for Chronic Myeloid Leukemia. Through significant suppression of the BCR-ABL auto-phosphorylation (EC50 about 100 nM) and downstream mediators such as STAT5, Crkl and ERK/’s phosphorylation, CHMFL-ABL-053 inhibited the proliferation of CML cell lines K562 (GI50 = 14 nM), KU812 (GI50 = 25 nM) and MEG-01 (GI50 = 16 nM).

Reference

1:J Med Chem. 2016 Mar 10;59(5):1984-2004. doi: 10.1021/acs.jmedchem.5b01618. Epub 2016 Feb 5. 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.Liang X,Liu X,Wang B,Zou F,Wang A,Qi S,Chen C,Zhao Z,Wang W,Qi Z,Lv F,Hu Z,Wang L,Zhang S,Liu Q,Liu J, PMID: 26789553 DOI: 10.1021/acs.jmedchem.5b01618 Abstract: Starting from a dihydropyrimidopyrimidine core scaffold based compound 27 (GNF-7), we discovered a highly potent (ABL1: IC50 of 70 nM) and selective (S score (1) = 0.02) BCR-ABL inhibitor 18a (CHMFL-ABL-053). Compound 18a did not exhibit apparent inhibitory activity against c-KIT kinase, which is the common target of currently clinically used BCR-ABL inhibitors. Through significant suppression of the BCR-ABL autophosphorylation (EC50 about 100 nM) and downstream mediators such as STAT5, Crkl, and ERK/’s phosphorylation, 18a inhibited the proliferation of CML cell lines K562 (GI50 = 14 nM), KU812 (GI50 = 25 nM), and MEG-01 (GI50 = 16 nM). A pharmacokinetic study revealed that 18a had over 4 h of half-life and 24% bioavailability in rats. A 50 mg/kg/day dosage treatment could almost completely suppress 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.