Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-<i>N</i>-methylpyridine-2-carboxamide (AZD5305): A PARP1–DNA Trapper with High Selectivity for PARP1 over PARP2 and Other PARPs

W. Johannes, Jeffrey; Balazs, Amber; Barratt, Derek; Biśta, Michał; D. Chuba, Matthew; Cosulich, Sabina; E. Critchlow, Susan; L. Degorce, Sébastien; Di Fruscia, Paolo; D. Edmondson, Scott; J. Embrey, Kevin; E. Fawell, Stephen; Ghosh, Avipsa; J. Gill, Sonja; Gunnarsson, Anders; M. Hande, Sudhir; D. Heightman, Tom; Hemsley, Paul; Illuzzi, Giuditta; Lane, Jordan; Larner, Carrie; Leo, Elisabetta; Liu, Lina; Madin, Andrew; Martin, Scott; McWilliams, Lisa; J. O’Connor, Mark; P. Orme, Jonathan; Pachl, Fiona; J. Packer, Martin; Pei, Xiaohui; Pike, Andrew; Schimpl, Marianne; She, Hongyao; D. Staniszewska, Anna; Talbot, Verity; Underwood, E.; Varnes, Jeffrey; Xue, Lin; Yao, Tieguang; Zhang, Ke; X. Zhang, Andrew; Zheng, Xiaolan

doi:10.1021/acs.jmedchem.1c01012

Public

Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-N-methylpyridine-2-carboxamide (AZD5305): A PARP1–DNA Trapper with High Selectivity for PARP1 over PARP2 and Other PARPs

Published in Journal of Medicinal Chemistry • Sep 27, 2021

Authors:

Jeffrey W. Johannes

Amber Balazs

Derek Barratt

Abstract

Poly-ADP-ribose-polymerase (PARP) inhibitors have achieved regulatory approval in oncology for homologous recombination repair deficient tumors including BRCA mutation. However, some have failed in combination with first-line chemotherapies, usually due to overlapping hematological toxicities. Curre...

Subject

PARP1

Poly ADP ribose polymerase

Chemistry

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