Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper.

Giuditta Illuzzi Anna D Staniszewska Sonja J Gill Andy Pike Lisa McWilliams Susan E Critchlow Anna Cronin Stephen E Fawell Glen Hawthorne Kunzah Jamal Jeffrey W Johannes Emilyanne Leonard Ruth Macdonald Gareth A Maglennon Jenni Nikkilä Lenka Oplustil O'Connor Aaron Smith Harriet Southgate Joanne Wilson James W T Yates Sabina Cosulich Elisabetta Leo

Published in: Clinical cancer research : an official journal of the American Association for Cancer Research (2022)

AZD5305 potently and selectively inhibits PARP1 resulting in excellent antiproliferative activity and unprecedented selectivity for DNA repair deficient versus proficient cells. These data confirm the hypothesis that targeting only PARP1 can retain the therapeutic benefit of nonselective PARPi, while reducing potential for hematotoxicity. AZD5305 is currently in phase I trials (NCT04644068).

Keyphrases

dna repair
dna damage
dna damage response
induced apoptosis
cell cycle arrest
electronic health record
big data
signaling pathway
cell therapy
stem cells
machine learning
risk assessment
climate change
pi k akt