Discovery and Optimization of a Series of Benzofuran Selective ERAP1 Inhibitors: Biochemical and
Journal
ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073
Informations de publication
Date de publication:
08 Jul 2021
08 Jul 2021
Historique:
received:
20
04
2021
accepted:
03
06
2021
entrez:
16
7
2021
pubmed:
17
7
2021
medline:
17
7
2021
Statut:
epublish
Résumé
ERAP1 is a key aminopeptidase involved in peptide trimming before major histocompatibility complex (MHC) presentation. A single nucleotide polymorphism (SNP) in the ERAP1 gene can lead to impaired trimming activity and affect ERAP1 function. ERAP1 genetic variations have been linked to an increased susceptibility to cancer and autoimmune disease. Here, we report the discovery of novel ERAP1 inhibitors using a high throughput screening approach. Due to ERAP1 broad substrate specificity, the hit finding strategy included testing inhibitors with a range of biochemical assays. Based on the hit potency, selectivity, and
Identifiants
pubmed: 34267884
doi: 10.1021/acsmedchemlett.1c00235
pmc: PMC8274102
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1137-1142Informations de copyright
© 2021 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
Références
Nat Immunol. 2002 Dec;3(12):1169-76
pubmed: 12436109
Hum Immunol. 2019 May;80(5):281-289
pubmed: 30419264
Nat Struct Mol Biol. 2011 May;18(5):604-13
pubmed: 21478864
Genes Immun. 2014 Dec;15(8):521-7
pubmed: 25142031
Proc Natl Acad Sci U S A. 2013 Dec 3;110(49):19890-5
pubmed: 24248368
Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17107-12
pubmed: 16286653
Mol Immunol. 2015 Oct;67(2 Pt B):426-35
pubmed: 26224046
J Med Chem. 2020 Jan 9;63(1):103-121
pubmed: 31841350
PLoS One. 2008;3(11):e3658
pubmed: 18987748
Mol Immunol. 2020 May;121:7-19
pubmed: 32135401
Nat Immunol. 2002 Dec;3(12):1177-84
pubmed: 12436110
Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):17594-9
pubmed: 25422414
J Med Chem. 2006 Oct 19;49(21):6177-96
pubmed: 17034125
Bioorg Med Chem Lett. 2016 Aug 15;26(16):4122-6
pubmed: 27390066
J Biomol Screen. 2002 Dec;7(6):531-40
pubmed: 14599351
J Chem Theory Comput. 2016 Jan 12;12(1):281-96
pubmed: 26584231
Anal Biochem. 2009 Dec 1;395(1):33-40
pubmed: 19638272
J Immunol. 2013 Jun 1;190(11):5839-46
pubmed: 23610143
Proc Natl Acad Sci U S A. 2019 Dec 16;:
pubmed: 31843903
J Immunol. 2011 Feb 15;186(4):1909-13
pubmed: 21242517