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Ref Type Journal Article
PMID (24837299)
Authors Tanaka H, Hirata M, Shinonome S, Wada T, Iguchi M, Dohi K, Inoue M, Ishioka Y, Hojo K, Yamada T, Sugimoto T, Masuno K, Nezasa K, Sato N, Matsuo K, Yonezawa S, Frenkel EP, Shichijo M
Title Preclinical antitumor activity of S-222611, an oral reversible tyrosine kinase inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2.
Journal Vol Issue Date Pages Journal Short Title
Cancer science 105 8 2014 Aug 1040-8 Cancer Sci
URL
Abstract Text 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 and could be effective against bone and brain metastasis. Compared to neratinib and afatinib, irreversible EGFR/HER2 inhibitors, S-222611 showed equivalent or slightly weaker antitumor activity but a safer profile. These results indicated that S-222611 is a potent EGFR and HER2 inhibitor with substantially better antitumor activity than lapatinib at clinically relevant doses. Considering the safer profile than for irreversible inhibitors, S-222611 could be an important option in future cancer therapy.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Epertinib Epertinib 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
Epertinib S-222611|S222611|S222611 EGFR Inhibitor (Pan) 61 HER2 Inhibitor 41 Epertinib (S-222611) is a dual inhibitor of EGFR and ERBB2 (HER2), leading to decreased kinase activity and potentially inhibiting growth of tumors expressing EGFR or ERBB2 (HER2) (PMID: 24837299, PMID: 30196106, PMID: 31892325).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References