ponatinib

Description: Ponatinib (formerly known as AP24534; trade name Iclusig) is a novel, orally bioavailable multi-targeted kinase inhibitor with potent antitumor activity. It inhibits Abl, PDGFRalpha, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM in cell-free assays, respectively. It has the potential for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL). Ponatinib inhibits unmutated and all mutated forms of Bcr-Abl, including T315I, the highly drug therapy-resistant missense mutation of Bcr-Abl. Ponatinib was approved by the US FDA on December 14, 2012, for patients with resistant or intolerant CML and Ph+ ALL.

References: Cancer Cell. 2009 Nov 6; 16(5):401-12; J Med Chem. 2010 Jun 24; 53(12):4701-19.

Related CAS: 1114544-31-8 (HCl); 1232836-25-7 (tris-hydrochloride); 943319-70-8 (free base)

Chemical Name: 3-(imidazo[1, 2-b]pyridazin-3-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide.

InChi Key: PHXJVRSECIGDHY-UHFFFAOYSA-N

InChi Code: InChI=1S/C29H27F3N6O/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)

SMILES Code: O=C(NC1=CC=C(CN2CCN(C)CC2)C(C(F)(F)F)=C1)C3=CC=C(C)C(C#CC4=CN=C5C=CC=NN54)=C3