Preclinical Characterization of AZD9574, a Blood-Brain Barrier Penetrant Inhibitor of PARP1.

Anna D Staniszewska Domenic Pilger Sonja J Gill Kunzah Jamal Natacha Bohin Sofia Guzzetti Jacob A Gordon Gregory Hamm Gill Mundin Giuditta Illuzzi Andy Pike Lisa McWilliams Gareth A Maglennon Jonathan Rose Glen Hawthorne Miguel A Cortés González Christer Halldin Peter Johnström Magnus Schou Susan E Critchlow Stephen E Fawell Jeffrey W Johannes Elisabetta Leo Barry R Davies Sabina Cosulich Jann N Sarkaria Lenka Oplustil O'Connor Petra Hamerlik

Published in: Clinical cancer research : an official journal of the American Association for Cancer Research (2023)

The combination of three key features - PARP1 selectivity, PARP1 trapping profile, and high CNS penetration in a single molecule, supports the development of AZD9574 as the best-in-class PARP inhibitor for the treatment of primary and secondary brain tumors. As documented by in vitro and in vivo studies, AZD9574 shows robust anti-cancer efficacy both as a single agent as well as in combination with TMZ. AZD9574 is currently in a phase I trial (NCT05417594).

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