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Updated: Apr 18, 2026

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
Structure-Based Drug Design of Novel, Potent, and Selective Azabenzimidazoles (ABI) as ATR Inhibitors
Paul A Barsanti1, Yue Pan1, Yipin Lu1
1Global Discovery Chemistry/Oncology, Novartis Institutes for Biomedical Research , 5300 Chiron Way, Emeryville, California 94608, United States.
Abstract:
Compound 13 was discovered through morphing of the ATR biochemical HTS hit 1. The ABI series was potent and selective for ATR. Incorporation of a 6-azaindole afforded a marked increase in cellular potency but was associated with poor PK and hERG ion channel inhibition. DMPK experiments established that CYP P450 and AO metabolism in conjunction with Pgp and BCRP efflux were major causative mechanisms for the observed PK. The series also harbored the CYP3A4 TDI liability driven by the presence of both a morpholine and an indole moiety. Incorporation of an adjacent fluorine or nitrogen into the 6-azaindole addressed many of the various medicinal chemistry issues encountered.
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