Structure, development, preclinical and clinical efficacy of tivozanib (KRN-951, AV-951).

Tivozanib hydrochloride monohydrate (tivozanib; formerly KRN-951, AV-951) is a potent pan-VEGF receptor tyrosine kinase inhibitor. The biological activity of tivozanib seems to outstand that of other VEGF tyrosine kinase inhibitors. In Phase I studies, observed side effects are generally mild, with hypertension being the most common adverse event. In single-agent Phase II and III studies in patients with advanced or metastatic renal cell carcinoma, tivozanib has demonstrated convincing clinical activity. Further clinical trials of tivozanib combined with various cytotoxic drug regimens as well as other classes of target-specific anticancer agents (e.g., mTOR inhibitors) for other indications are underway. Tivozanib has not yet been approved for regular use.