BRIGATINIB ANALOG

Description: Brigatinib analog, an analog of Brigatinib (formerly known as AP-26113) which is an orally bioavailable, potent and selective ALK inhibitor with IC50 of 0.62 nM in a cell-free assay, it demonstrated the ability to overcome crizotinib resistance mediated by a L1196M mutation. Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor which has been implicated in numerous solid and hematologic cancers. ALK mutations are reported in about 5-7% of neuroblastoma cases but the ALK-positive percentage increases significantly in the relapsed patient population. AP26113 analog binds to and inhibits ALK kinase and ALK fusion proteins as well as EGFR and mutant forms. This leads to the inhibition of ALK kinase and EGFR kinase, disrupts their signaling pathways and eventually inhibits tumor cell growth in susceptible tumor cells. Brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial.

References: Proc Natl Acad Sci U S A. 2011 May 3; 108(18):7535-40; J Med Chem. 2016 May 26; 59(10):4948-64; Oncotarget. 2016 May 17; 7(20):29011-22.

Related CAS: 1197953-54-0 (Brigatinib)

Chemical Name: (2-((5-chloro-2-((4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide

InChi Key: OVDSPTSBIQCAIN-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H34ClN6O2P/c1-32(2)18-12-14-33(15-13-18)19-10-11-21(23(16-19)35-3)30-26-28-17-20(27)25(31-26)29-22-8-6-7-9-24(22)36(4, 5)34/h6-11, 16-18H, 12-15H2, 1-5H3, (H2, 28, 29, 30, 31)

SMILES Code: CP(C)(C1=CC=CC=C1NC2=NC(NC3=CC=C(N4CCC(N(C)C)CC4)C=C3OC)=NC=C2Cl)=O