Rociletinib (CNX-419) is an orally available small molecule, irreversible inhibitor of epidermal growth factor receptor (EGFR) with potential antineoplastic activity.

EGFR (WT):303.3 nM(Ki), EGFR (L858R/T790M):21.5 nM(Ki)

CO-1686在所有EGFR突变体模型以及表达EGFRL858R-和EGFRL858R/T790M的转基因小鼠中引起显著的剂量依赖性肿瘤生长抑制.

CO-1686选择性抑制NSCLC细胞表达的突变体EGFR的生长,GI50范围为7 到 32 nM,并诱导细胞凋亡。耐CO-1686的NSCLC细胞系表现出上皮 - 间充质转变的迹象并且对AKT抑制剂的敏感性增加。CO-1686在表达突变型EGFR的细胞中抑制p-EGFR,其IC50范围为62至187 nM,同时在三种WT EGFR表达细胞中抑制EGFR磷酸化,IC50> 2,000 nM。

Inhibition Kinetics Studies: Recombinant human wild-type and T790M/L858R double mutant EGFR, both Nterminal GST-tagged, are used in the assay. The Omnia continuous read assay is performed as described by the vendor.

Cells are seeded at 3,000 cells per well in growth media supplemented with 5% FBS, 2 mmol/L, L-glutamine, and 1% penicillin–streptomycin, allowed to adhere overnight, and treated with a dilution series of test compounds for 72 hours. Cell viability is determined by CellTiter-Glo, and results are represented as background-subtracted relative light units normalized to a dimethyl sulfoxide (DMSO)–treated control. Growth inhibition (GI 50) values are determined by GraphPad Prism 5.04. MK-2206 and XL-880 compounds are obtained from Selleck Chemical. CI data are generated using CalcuSyn.(Only for Reference)