Robin R Frey, Navendu Jana, Jacob V Gorman, Jin Wang, Heath A Smith, Kenneth D Bromberg, Ashish Thakur, Stella Z Doktor, Anura S Indulkar, Clarissa G Jakob, Anup K Upadhyay, Wei Qiu, Vlasios Manaves, Frank Gambino, Stephen A Valentino, Debra Montgomery, Yebin Zhou, Tao Li, Fritz G Buchanan, Debra C Ferguson, Matthew D Kurnick, Nicolas Kapecki, Albert Lai, Michael R Michaelides, Thomas D Penning
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Discovery of Potent Azetidine-Benzoxazole MerTK Inhibitors with In Vivo Target Engagement.
Inhibition of the receptor tyrosine kinase MerTK by small molecules has the potential to augment the immune response to tumors. Potent, selective inhibitors with high levels of in vivo target engagement are needed to fully evaluate the potential use of MerTK inhibitors as cancer therapeutics. We report the discovery and optimization of a series of pyrazinamide-based type 1.5 MerTK inhibitors bearing an azetidine-benzoxazole substituent. Compound 31 potently engages the target in vivo and demonstrates single agent activity in the immune-driven MC-38 murine syngeneic tumor model.
期刊介绍：
The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents.
The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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