Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Fusion Lumos
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: Dingyin Tao
LAB HEAD: Dingyin Tao
PROVIDER: PXD030140 | Pride | 2025-05-06
REPOSITORIES: Pride
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Rana Sandeep S Dranchak Patricia P Dahlin Jayme L JL Lamy Laurence L Li Wenqing W Oliphant Erin E Shrimp Jonathan H JH Rajacharya Girish H GH Tharakan Ravi R Holland David O DO Whitten Apryl S AS Wilson Kelli M KM Singh Pankaj K PK Durum Scott K SK Tao Dingyin D Rai Ganesha G Inglese James J
Cell chemical biology 20231023 2
Methotrexate (MTX) is a tight-binding dihydrofolate reductase (DHFR) inhibitor, used as both an antineoplastic and immunosuppressant therapeutic. MTX, like folate undergoes folylpolyglutamate synthetase-mediated γ-glutamylation, which affects cellular retention and target specificity. Mechanisms of MTX resistance in cancers include a decrease in MTX poly-γ-glutamylation and an upregulation of DHFR. Here, we report a series of potent MTX-based proteolysis targeting chimeras (PROTACs) to investiga ...[more]