Preclinical antitumor activity of S-222611, an oral reversible tyrosine kinase inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2.
Bottom Line: 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.
Affiliation: Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.Show MeSH
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Mentions: We evaluated S-222611 in patient-oriented models. Because bone metastasis is observed in more than 80% of advanced breast cancer patients with significant morbidity, we examined S-222611 using a model of luciferase-expressing human breast cancer cells implanted into the femur of nude mice.(30) S-222611 showed approximately four times more potent activity than lapatinib and completely inhibited the growth of cancer cells at 50 mg/kg (Fig. 3a,b).
Affiliation: Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.