Identification of a Novel KAT6A/B Inhibitor with Enhanced Antitumor Activity and Reduced Hematologic Toxicity
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R Liu
Cancer Research, 2025
xfsjsgc.com
Background: KAT6A/B are promising therapeutic targets in breast cancer. However, Phase I data of PF-07248144 revealed significant treatment-related neutropenia (≥ Grade 3 in 38.3% of patients), including Grade 4 events, which emerged as the primary dose-limiting toxicity. To address this challenge, this project focuses on developing highly selective KAT6A/B inhibitors with a" fast-on, fast-off" pharmacokinetic profile to maximize antitumor activity while mitigating hematopoietic toxicity. Methods:
