compound 33a [PMID: 35944901]   Click here for help

GtoPdb Ligand ID: 12126

Compound class: Synthetic organic
Comment: This compound is an inhibitor of the ongogenic BCR-Abl kinase, that was designed to decrease cardiotoxicity compared to existing therapeutics in this class, such as ponatinib [1]. Like ponatinib, 33a potently inhibits both wild type BCR-Abl and mutant BCR-Abl kinase that expresses the gatekeeper resistance mutation T315I. Ponatinib is currently (August 2022) the only Abl kinase inhibitor that is effective in CML with the BCR-AblT315I mutation.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 76.59
Molecular weight 486.14
XLogP 5.61
No. Lipinski's rules broken 1
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Canonical SMILES O=C(c1ccc(c(c1)C#Cc1cnc2n1nccc2)C)Nc1cc(cc(c1)C(F)(F)F)n1ccnc1
Isomeric SMILES Cc1c(C#Cc2cnc3cccnn23)cc(C(=O)Nc2cc(C(F)(F)F)cc(n3cncc3)c2)cc1
InChI InChI=1S/C26H17F3N6O/c1-17-4-5-19(11-18(17)6-7-22-15-31-24-3-2-8-32-35(22)24)25(36)33-21-12-20(26(27,28)29)13-23(14-21)34-10-9-30-16-34/h2-5,8-16H,1H3,(H,33,36)
1. Pandrala M, Bruyneel AAN, Hnatiuk AP, Mercola M, Malhotra SV. (2022)
Designing Novel BCR-ABL Inhibitors for Chronic Myeloid Leukemia with Improved Cardiac Safety.
J Med Chem, 65 (16): 10898-10919. [PMID:35944901]