Brigatinib (AP26113)

Description: Brigatinib (formerly known as AP-26113 (ALK-IN-1); trade name: Alunbrig) is an orally bioavailable, highly potent and selective anaplastic lymphoma kinase-ALK inhibitor with potential antineoplastic activity. It inhibits ALK with an IC50 of 0.62 nM in a cell-free assay. Brigatinib demonstrated the ability to overcome crizotinib resistance mediated by a L1196M mutation. Brigatinib has been approved be FDA in 2017 to treat patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. 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; 1197958-12-5 (Brigatinib analog)

AP-26113; AP 26113; Brigatinib-analog; AP26113; Brigatinib; Alunbrig.

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

InChi Key: AILRADAXUVEEIR-UHFFFAOYSA-N

InChi Code: InChI=1S/C29H39ClN7O2P/c1-35-15-17-37(18-16-35)21-11-13-36(14-12-21)22-9-10-24(26(19-22)39-2)33-29-31-20-23(30)28(34-29)32-25-7-5-6-8-27(25)40(3, 4)38/h5-10, 19-21H, 11-18H2, 1-4H3, (H2, 31, 32, 33, 34)

SMILES Code: CN1CCN(C2CCN(C3=CC=C(NC4=NC=C(Cl)C(NC5=CC=CC=C5P(C)(C)=O)=N4)C(OC)=C3)CC2)CC1