Structure-Based Discovery of Proline-Derived Arginase Inhibitors with Improved Oral Bioavailability for Immuno-Oncology

Min Lu(Merck & Co., Inc., Rahway, NJ, USA (United States)), Hongjun Zhang(Merck & Co., Inc., Rahway, NJ, USA (United States)), Derun Li(Merck & Co., Inc., Rahway, NJ, USA (United States)), Matthew C. Childers(Merck & Co., Inc., Rahway, NJ, USA (United States)), Qinglin Pu(Merck & Co., Inc., Rahway, NJ, USA (United States)), R.L. Palte(Merck & Co., Inc., Rahway, NJ, USA (United States)), Symon Gathiaka(Merck & Co., Inc., Rahway, NJ, USA (United States)), Thomas W. Lyons(Merck & Co., Inc., Rahway, NJ, USA (United States)), Anandan Palani(Merck & Co., Inc., Rahway, NJ, USA (United States)), Peter W. Fan(Merck & Co., Inc., Rahway, NJ, USA (United States)), Peter Spacciapoli(Quantitative BioSciences), J. Richard Miller(Quantitative BioSciences), Hyelim Cho(Quantitative BioSciences), Mangeng Cheng(Quantitative BioSciences), Kalyan Chakravarthy(Quantitative BioSciences), Jennifer O’Neil(Merck & Co., Inc., Rahway, NJ, USA (United States)), Padmanabhan Eangoor(Merck & Co., Inc., Rahway, NJ, USA (United States)), Adam Beard(Merck & Co., Inc., Rahway, NJ, USA (United States)), Hai‐Young Kim(Merck & Co., Inc., Rahway, NJ, USA (United States)), Josep Saurí(Merck & Co., Inc., Rahway, NJ, USA (United States)), Hakan Günaydin(Merck & Co., Inc., Rahway, NJ, USA (United States)), David L. Sloman(Merck & Co., Inc., Rahway, NJ, USA (United States)), Phieng Siliphaivanh(Merck & Co., Inc., Rahway, NJ, USA (United States)), Jared N. Cumming(Merck & Co., Inc., Rahway, NJ, USA (United States)), Christian Fischer(Merck & Co., Inc., Rahway, NJ, USA (United States))
ACS Medicinal Chemistry Letters
July 16, 2021
Cited by 25Open Access
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Abstract

was well tolerated following multiple days of dosing at concentrations that exceed those required for serum arginase inhibition and concomitant arginine elevation in a syngeneic mouse carcinoma model.


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