| http://purl.uniprot.org/citations/36383674 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36383674 | http://www.w3.org/2000/01/rdf-schema#comment | "6-Diazo-5-oxo-l-norleucine (DON) is a glutamine antagonist that suppresses cancer cell metabolism but concurrently enhances the metabolic fitness of tumor CD8+ T cells. DON showed promising efficacy in clinical trials; however, its development was halted by dose-limiting gastrointestinal (GI) toxicities. Given its clinical potential, we designed DON peptide prodrugs and found DRP-104 [isopropyl(S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)-propanamido)-6-diazo-5-oxo-hexanoate] that was preferentially bioactivated to DON in tumor while bioinactivated to an inert metabolite in GI tissues. In drug distribution studies, DRP-104 delivered a prodigious 11-fold greater exposure of DON to tumor versus GI tissues. DRP-104 affected multiple metabolic pathways in tumor, including decreased glutamine flux into the TCA cycle. In efficacy studies, both DRP-104 and DON caused complete tumor regression; however, DRP-104 had a markedly improved tolerability profile. DRP-104's effect was CD8+ T cell dependent and resulted in robust immunologic memory. DRP-104 represents a first-in-class prodrug with differential metabolism in target versus toxicity tissue. DRP-104 is now in clinical trials under the FDA Fast Track designation."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.org/dc/terms/identifier | "doi:10.1126/sciadv.abq5925"xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Pal A."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Wu Y."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Zhao L."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Pandey R."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Lam J."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Alt J."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Majer P."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Lemberg K.M."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Slusher B.S."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Powell J.D."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Arwood M.L."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Thomas A.G."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Seiwert T."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Peters D.E."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Rais R."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Dash R.P."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Tallon C."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Leone R.D."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Tenora L."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/author | "Aguilar J.M.H."xsd:string |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/36383674 | http://purl.uniprot.org/core/name | "Sci Adv"xsd:string |