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dc.contributor.authorWilding, B
dc.contributor.authorPasqua, AE
dc.contributor.authorE A Chessum, N
dc.contributor.authorPierrat, OA
dc.contributor.authorHahner, T
dc.contributor.authorTomlin, K
dc.contributor.authorShehu, E
dc.contributor.authorBurke, R
dc.contributor.authorRichards, GM
dc.contributor.authorWhitton, B
dc.contributor.authorArwert, EN
dc.contributor.authorThapaliya, A
dc.contributor.authorSalimraj, R
dc.contributor.authorvan Montfort, R
dc.contributor.authorSkawinska, A
dc.contributor.authorHayes, A
dc.contributor.authorRaynaud, F
dc.contributor.authorChopra, R
dc.contributor.authorJones, K
dc.contributor.authorNewton, G
dc.contributor.authorCheeseman, MD
dc.date.accessioned2021-09-07T08:32:57Z
dc.date.available2021-09-07T08:32:57Z
dc.date.issued2021-06-15
dc.identifier.citationBioorganic & medicinal chemistry letters, 2021, 42 pp. 128050 - ?
dc.identifier.issn0960-894X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4794
dc.identifier.eissn1464-3405
dc.identifier.doi10.1016/j.bmcl.2021.128050
dc.description.abstractERAP1 is a zinc-dependent M1-aminopeptidase that trims lipophilic amino acids from the N-terminus of peptides. Owing to its importance in the processing of antigens and regulation of the adaptive immune response, dysregulation of the highly polymorphic ERAP1 has been implicated in autoimmune disease and cancer. To test this hypothesis and establish the role of ERAP1 in these disease areas, high affinity, cell permeable and selective chemical probes are essential. DG013A 1, is a phosphinic acid tripeptide mimetic inhibitor with reported low nanomolar affinity for ERAP1. However, this chemotype is a privileged structure for binding to various metal-dependent peptidases and contains a highly charged phosphinic acid moiety, so it was unclear whether it would display the high selectivity and passive permeability required for a chemical probe. Therefore, we designed a new stereoselective route to synthesize a library of DG013A 1 analogues to determine the suitability of this compound as a cellular chemical probe to validate ERAP1 as a drug discovery target.
dc.formatPrint-Electronic
dc.format.extent128050 - ?
dc.languageeng
dc.language.isoeng
dc.publisherPERGAMON-ELSEVIER SCIENCE LTD
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleInvestigating the phosphinic acid tripeptide mimetic DG013A as a tool compound inhibitor of the M1-aminopeptidase ERAP1.
dc.typeJournal Article
dcterms.dateAccepted2021-04-13
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1016/j.bmcl.2021.128050
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBioorganic & medicinal chemistry letters
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Hit Discovery & Structural Design
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 3
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology/Hit Discovery & Structural Design
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Hit Discovery & Structural Design
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 3
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology/Hit Discovery & Structural Design
pubs.publication-statusPublished
pubs.volume42
pubs.embargo.termsNot known
icr.researchteamClinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
icr.researchteamMedicinal Chemistry 3
icr.researchteamHit Discovery & Structural Design
icr.researchteamClinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
icr.researchteamMedicinal Chemistry 3
icr.researchteamHit Discovery & Structural Design
dc.contributor.icrauthorPierrat, Olivier
dc.contributor.icrauthorHahner, Tamas
dc.contributor.icrauthorBurke, Rosemary
dc.contributor.icrauthorArwert, Esther
dc.contributor.icrauthorThapaliya, Arjun
dc.contributor.icrauthorSalimraj, Ramya
dc.contributor.icrauthorVan Montfort, Robert
dc.contributor.icrauthorRaynaud, Florence
dc.contributor.icrauthorNewton, Gary
dc.contributor.icrauthorCheeseman, Matthew


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