Preclinical antitumor activity of S-222611, an oral reversible tyrosine kinase inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2.

ABSTRACT: Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are validated molecular targets in cancer therapy. Dual blockade has been explored and one such agent, lapatinib, is in clinical practice but with modest activity. Through chemical screening, we discovered a novel EGFR and HER2 inhibitor, S-222611, that selectively inhibited both kinases with IC50 s below 10 nmol/L. S-222611 also inhibited intracellular kinase activity and the growth of EGFR-expressing and HER2-expressing cancer cells. In addition, S-222611 showed potent antitumor activity over lapatinib in a variety of xenograft models. In evaluations with two patient-oriented models, the intrafemoral implantation model and the intracranial implantation model, S-222611 exhibited excellent activity

SUBMITTER: Tanaka H 

PROVIDER: S-EPMC4317859 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature