Aurora Kinase specific therapeutics in oncology

Green MR, Woolery JE, Mahadevan D "EXPERT Opinion ON DRUG DISCOVERY MAR 2011"

Introduction:

Mammalian cells include 3 unique serine/threonine protein kinases with highly conserved catalytic domains, which includes aurora A and B kinases which are important regulators of mitotic entry and progression. Overexpression of aurora A and/or B kinase is related to large proliferation rates and poor prognosis, making them ideal targets for anticancer treatment. Disruption of mitotic machinery is really a confirmed anticancer method utilised by many chemotherapeutic agents. Quite a few small molecule inhibitors with the aurora kinases happen to be discovered and examined in vivo and in vitro, using a few presently in Stage II testing.

Areas covered:

This evaluation gives the reader with up-to-date final results from both preclinical and human scientific studies for every of the aurora kinase inhibitors (AKIs) which are currently becoming investigated. The paper also covers in detail the late breaking and Stage I data introduced for AKIs thus allowing the reader to evaluate and distinction person and class-related consequences of AKIs.

Expert viewpoint:

While the profitable development and approval of an AKI for anticancer treatment stays unresolved, preclinical identification of resistant mechanisms would aid in creating greater early phase clinical trials where pertinent combos may possibly be evaluated before Phase II screening. The authors believe that aurora kinases are critical anticancer targets that run in collaboration with other oncogenes intimately involved in uncontrolled tumor proliferation and by offering a special, focused and complimentary anticancer mechanism, broaden the accessible armamentarium towards cancer.