Drugging ATR: Progress in the Development of Specific Inhibitors for the Treatment of Cancer

Citations Over TimeTop 10% of 2015 papers

Abstract

In this article, we review the ATR inhibitor field from initial pharmacological tools to first-generation clinical candidates with the potential to bring benefit to cancer patients. ATR is a critical part of the cell DNA-damage response. Over the past decade or more, compounds with weak ATR potency and low specificity have been used as tools in early studies to elucidate ATR pharmacology. More recently highly potent, selective and in vivo active ATR inhibitors have been developed enabling detailed preclinical in vitro and in vivo target assessment to be made. The published studies reveal the potential of ATR inhibitors for use as monotherapy or in combination with DNA-damaging agents. To date, VX-970 and AZD6738, have entered clinical assessment.

Related Papers

• → A comparison of in vivo and in vitro methods for determining availability of iron from meals(1981)109 cited
• → Examination of the Utility of the High Throughput In Vitro Metabolic Stability Assay to Estimate In Vivo Clearance in the Mouse(2009)10 cited
• → Studies on pharmacokinetics of sulfonated aluminum phthalocyanine in a transplantable mouse tumor by in vivo fluorescence(1993)8 cited
• Combination antifol therapy: observations on the development of resistant L1210 leukemic cells in vivo.(1980)
• → In vivo bioactivities and kinetic parameters of rat luteinizing hormone components: discrepancy between in vitro and in vivo assays(ラット黄体形成ホルモン分子種のin vivo生物活性と動態学的パラメーター: in vitroアッセイとin vivoアッセイの矛盾)(1998)