Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5-<i>a</i>]pyridine Scaffold: SAR of the Aryloxyaryl Moiety
Stefano Sainas, Marta Giorgis, Paola Circosta, Giulio Poli, Marta Alberti, Alice Passoni, Valentina Gaidano, Agnese Chiara Pippione, Nicoletta Vitale, Davide Bonanni, Barbara Rolando, Alessandro Cignetti, Cristina Ramondetti, Alessia Lanno, Davide M. Ferraris, Barbara Canepa, Barbara Buccinnà, Marco Piccinini, Menico Rizzi, Giuseppe Saglio, Salam Al‐Karadaghi, Donatella Boschi, Riccardo Miggiano, Tiziano Tuccinardi, Marco L. Lolli
Abstract
has an extremely low cytotoxicity on non-AML cells as well as MEDS433; it has shown a significant antileukemic activity in vivo in a xenograft mouse model of AML.
Topics & Concepts
ChemistryDihydroorotate dehydrogenaseMoietyIn vivoIC50LeukemiaCytotoxicityScaffoldIn vitroPharmacologyStereochemistryBiochemistryPyrimidineImmunologyBiologyMedicineBiomedical engineeringBiotechnologyBiochemical and Molecular ResearchHIV/AIDS drug development and treatmentCytomegalovirus and herpesvirus research