Structure-Based Discovery of Proline-Derived Arginase Inhibitors with Improved Oral Bioavailability for Immuno-Oncology
Min Lu, Hongjun Zhang, Derun Li, Matthew C. Childers, Qinglin Pu, R.L. Palte, Symon Gathiaka, Thomas W. Lyons, Anandan Palani, Peter W. Fan, Peter Spacciapoli, J. Richard Miller, Hyelim Cho, Mangeng Cheng, Kalyan Chakravarthy, Jennifer O’Neil, Padmanabhan Eangoor, Adam Beard, Hai‐Young Kim, Josep Saurí, Hakan Günaydin, David L. Sloman, Phieng Siliphaivanh, Jared N. Cumming, Christian Fischer
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.
Topics & Concepts
ArginaseBioavailabilityDosingPharmacologyDrugConcomitantChemistryDrug discoveryPotencyMedicineArginineIn vitroBiochemistryAmino acidInternal medicineClick Chemistry and ApplicationsChemical Synthesis and AnalysisAdenosine and Purinergic Signaling