Novel, Potent, and Druglike Tetrahydroquinazoline Inhibitor That Is Highly Selective for Human Topoisomerase II α over β
José Antonio Ortega, José M. Arencibia, Elirosa Minniti, Jo Ann W. Byl, Sebastián Franco-Ulloa, Marco Borgogno, Vito Genna, Maria Summa, Sine Mandrup Bertozzi, Rosalia Bertorelli, Andrea Armirotti, Anna Minarini, Claudia Sissi, Neil Osheroff, Marco De Vivo
Abstract
= 120 μM for the anticancer drug etoposide] with excellent metabolic stability and solubility. This new compound also shows ~100-fold selectivity for topoIIα over topoβ, a broad antiproliferative activity toward cultured human cancer cells, a favorable in vivo pharmacokinetic profile, and the ability to penetrate the blood-brain barrier. Thus, ARN-21934 is a highly promising lead for the development of novel and potentially safer topoII-targeted anticancer drugs.
Topics & Concepts
ChemistryTopoisomeraseEtoposideIn vivoTopoisomerase inhibitorPharmacologyIC50DrugDNAIn vitroBiochemistryBiologyChemotherapyGeneticsBiotechnologyCancer therapeutics and mechanismsLung Cancer Research StudiesNeutropenia and Cancer Infections