Icotinib (BPI2009)

Description: Icotinib (formerly known as BPI-2009; trade name Conmana), a side chain-cyclized form of erlotinib, is an orally available and specific EGFR inhibitor with potent anticancer activity. Icotinib is structurally similar to erlotinib and was approved in China to treat lung cancer (NSCLC) in 2011. It inhibits EGFR with an IC50 of 5 nM, including the EGFR, EGFR(L858R), EGFR(L861Q), EGFR(T790M) and EGFR(T790M, L858R). When profiled with 88 kinases, Icotinib only showed meaningful inhibitory activity to EGFR and its mutants. Icotinib blocked EGFR-mediated intracellular tyrosine phosphorylation (IC50?=?45?nM) in the human epidermoid carcinoma A431 cell line and inhibits tumor cell proliferation. In vivo studies demonstrated that Icotinib exhibited potent dose-dependent antitumor effects in nude mice carrying a variety of human tumor-derived xenografts. The drug was well tolerated at doses up to 120?mg/kg/day in mice without mortality or significant body weight loss during the treatment. A head to head randomized, double blind phase III trial using Gefitinib as an active control for patients with advanced non-small cell lung cancer (NSCLC) was finished recently (Trial registration ID: NCT01040780). The data shows that Icotinib was non-inferior to Gefitinib in terms of median progression free survival (PFS) and safety superior favor to Icotinib compared to Gefitinib.

References: Lung Cancer. 2012 May; 76(2):177-82.

Related CAS: 610798-31-7 (free base); 1204313-51-8 (HCl)

Chemical Name: N-(3-ethynylphenyl)-7, 8, 10, 11, 13, 14-hexahydro-[1, 4, 7, 10]tetraoxacyclododecino[2, 3-g]quinazolin-4-amine hydrochloride

InChi Key: PNNGXMJMUUJHAV-UHFFFAOYSA-N

InChi Code: InChI=1S/C22H21N3O4.ClH/c1-2-16-4-3-5-17(12-16)25-22-18-13-20-21(14-19(18)23-15-24-22)29-11-9-27-7-6-26-8-10-28-20; /h1, 3-5, 12-15H, 6-11H2, (H, 23, 24, 25); 1H

SMILES Code: C#CC1=CC(NC2=C3C=C(OCCOCCOCCO4)C4=CC3=NC=N2)=CC=C1.[H]Cl