E-7090 is a novel selective inhibitor of fibroblast growth factor receptors, that displays potent anti-tumor activity. It is a promising candidate as a therapeutic agent for the treatment of tumors harboring FGFR genetic abnormalities. E-7090 is an orally available and selective inhibitor of the tyrosine kinase activities of FGFR1, -2, and -3. In kinetic analyses E-7090 associated more rapidly with FGFR1 than did the type II FGFR1 inhibitor ponatinib, and E-7090 dissociated more slowly from FGFR1, with a relatively longer residence time, than did the type I FGFR1 inhibitor AZD4547, suggesting that its kinetics are more similar to the type V inhibitors, such as lenvatinib. E-7090 showed selective antiproliferative activity against cancer cell lines harboring FGFR genetic abnormalities and decreased tumor size in a mouse xenograft model using cell lines with dysregulated FGFR. Furthermore, E-7090 administration significantly prolonged the survival of mice with metastasized tumors in the lung. It is being investigated in a Phase I clinical trial for treatment of patients with solid tumors.

Ciprokinen is a renin inhibitor discovered by Roche. Ciprokinen inhibited human renin in a buffer and human plasma with an IC50 of 0.07 and 0.65 nmol/L, respectively. In animal models, acute and chronic administration of ciprokinen lead to a reduction in arterial blood pressure. Development of ciprokinen was discontinued at a preclinical stage.

PF-05241328 is a novel, potent and selective inhibitor of human Nav1.7 voltage-dependent sodium channels (Nav1.7). It was developed for the pain treatment. It is highly plasma protein bound. PF-05241328 was ruled out based on half-life as the peak to trough ratios for this compound on twice-daily administration would require high therapeutic indices.