Ponatinib (hydrochloride)

Ponatinib is an orally bioavailable Bcr-Abl tyrosine kinase inhibitor (IC50 = 0.37 nM). It inhibits the tyrosine kinase inhibitor-resistant mutant Bcr-AblT315I (IC50 = 2 nM), as well as Bcr-AblQ252H, Bcr-AblY253F, Bcr-AblM351T, and Bcr-AblH396P mutants (IC50s = 0.44, 0.3, 0.3, and 0.34 nM, respectively). It is selective for Bcr-Abl and these mutants over the insulin receptor, IGF-1R, Aurora A kinase, and Cdk2/cyclin E but does inhibit the receptor tyrosine kinases c-Src, VEGF receptor 2 (VEGFR2), FGFR1, and PDGFRalpha (IC50s = 5.4, 1.5, 2.2, and 1.1 nM, respectively). Ponatinib inhibits proliferation of Ba/F3 cells expressing native (IC50 = 0.5 nM) or mutant Bcr-Abl (IC50s = 0.5-36 nM) and induces apoptosis. It reduces tumor growth in a Ba/F3 Bcr-AblT315I mouse xenograft model when administered at doses ranging from 10 to 30 mg/kg. Formulations containing ponatinib have been used in the treatment of chronic-, accelerated-, or blast-phase chronic myeloid leukemia (CML), T315I-positive CML, or T315I-positive Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL).Formal Name: 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-benzamide, monohydrochloride. CAS Number: 1114544-31-8. Synonyms: AP 24534. Molecular Formula: C29H27F3N6O . HCl. Formula Weight: 569.0. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMF: 2 mg/ml, DMSO: 11 mg/ml, Ethanol: Slightly soluble. lambdamax: 259, 267, 290, 301, 321 nm. SMILES: O=C(C1=CC=C(C)C(C#CC2=CN=C3C=CC=NN23)=C1)N([H])C4=CC=C(CN5CCN(CC5)C)C(C(F)(F)F)=C4.Cl. InChi Code: InChI=1S/C29H27F3N6O.ClH/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37,/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39),1H. InChi Key: BWTNNZPNKQIADY-UHFFFAOYSA-N.