Volasertib. Serine/threonine-protein kinase PLK1 inhibitor oncolytic

摘要

The dihydropteridinone derivative volasertib (BI-6727) is a second-inclass kinase inhibitor targeting serine/threonine-protein kinase PLK1 and developed by Boehringer Ingelheim. PLK1 is a major regulator of the cell cycle, which is overexpressed in proliferating tissues and in all cancer cell types analyzed today. In addition, PLK1 has turned out to be a negative prognostic and predictive marker for cancer patients. Thus, PLK1 is a promising target for the development of new anticancer therapeutics. Preclinical and phase I/II studies showed good tolerability for volasertib and demonstrated preliminary antitumor activity, as well as a good pharmacokinetic profile. The reported drug-related adverse events were mainly anemia, neutropenia and thrombocytopenia, and these three main side effects constitute the majority of dose-limiting events. Efficacy and safety data which have been reported to date for volasertib recommend the further development of the small-molecule compound. In general, the use of small-molecule kinase inhibitors targeting PLK1 should be regarded as a powerful approach for future cancer therapy.