Discovery and Development of Cyclic Peptide Inhibitors of CIB1.
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:
11 Nov 2021
11 Nov 2021
Historique:
received:
12
08
2021
accepted:
22
10
2021
entrez:
19
11
2021
pubmed:
20
11
2021
medline:
20
11
2021
Statut:
epublish
Résumé
Calcium and integrin binding protein 1 (CIB1) is a small, intracellular protein recently implicated in survival and proliferation of triple-negative breast cancer (TNBC). Considering its interactions with PAK1 and downstream signaling, CIB1 has been suggested as a potential therapeutic target in TNBC. As such, CIB1 has been the focus of inhibitor discovery efforts. To overcome issues of potency and stability in previously reported CIB1 inhibitors, we deploy mRNA display to discover new cyclic peptide inhibitors with improved biophysical properties and cellular activity. We advance UNC10245131, a cyclic peptide with low nanomolar affinity and good selectivity for CIB1 over other EF-hand domain proteins and improved permeability and stability over previously identified linear peptide inhibitor UNC10245092. Unlike UNC10245092, UNC10245131 lacks cytotoxicity and does not affect downstream signaling. Despite this, UNC10245131 is a potent ligand that could aid in clarifying roles of CIB1 in TNBC survival and proliferation and other CIB1-associated biological phenotypes.
Identifiants
pubmed: 34795874
doi: 10.1021/acsmedchemlett.1c00438
pmc: PMC8591747
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1832-1839Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM133107
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM125005
Pays : United States
Informations de copyright
© 2021 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
Références
Curr Opin Chem Biol. 2012 Apr;16(1-2):196-203
pubmed: 22401851
Breast Cancer Res Treat. 2015 Jul;152(2):337-46
pubmed: 26105795
Oncogene. 2013 Aug 22;32(34):4017-27
pubmed: 22964641
J Am Chem Soc. 2018 Sep 12;140(36):11360-11369
pubmed: 30118219
Adv Drug Deliv Rev. 2016 Jun 1;101:42-61
pubmed: 27067608
J Cell Biochem. 2011 Nov;112(11):3289-99
pubmed: 21748785
Eur J Med Chem. 2015 Apr 13;94:459-70
pubmed: 25591543
J Am Chem Soc. 2012 Feb 29;134(8):3864-72
pubmed: 22283712
Nat Chem Biol. 2016 Dec;12(12):1065-1074
pubmed: 27748751
J Biol Chem. 2006 Sep 8;281(36):26455-64
pubmed: 16825200
J Cell Biol. 2006 Jan 16;172(2):169-75
pubmed: 16418530
J Biol Chem. 2006 Jul 28;281(30):20825-20833
pubmed: 16723353
J Thromb Haemost. 2009 Nov;7(11):1906-14
pubmed: 19691476
J Cell Biol. 2005 Aug 1;170(3):465-76
pubmed: 16061695
Cell Death Dis. 2014 Apr 17;5:e1188
pubmed: 24743743
Nat Methods. 2006 May;3(5):357-9
pubmed: 16628205
Curr Pharm Des. 2010;16(28):3185-203
pubmed: 20687878
Biopolymers. 2015 Sep;104(5):453-61
pubmed: 25968458
J Biol Chem. 2011 May 13;286(19):17181-92
pubmed: 21388953
FASEB J. 2016 Aug;30(8):2640-50
pubmed: 27118676
Blood. 2012 Jan 19;119(3):838-46
pubmed: 22128142
Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17389-94
pubmed: 19805025
Angew Chem Int Ed Engl. 2018 Sep 10;57(37):11868-11881
pubmed: 29740917
Protein Sci. 2005 May;14(5):1214-21
pubmed: 15840829
J Biol Chem. 2005 Mar 4;280(9):8407-15
pubmed: 15574431
Biochemistry. 2013 Oct 8;52(40):7082-90
pubmed: 24011356
ACS Chem Biol. 2008 Feb 15;3(2):120-9
pubmed: 18215017
Nat Protoc. 2011 Jun;6(6):779-90
pubmed: 21637198
J Biol Chem. 1997 Feb 21;272(8):4651-4
pubmed: 9030514
ACS Chem Biol. 2020 Jun 19;15(6):1505-1516
pubmed: 32383857
J Biol Chem. 2002 Aug 9;277(32):28877-83
pubmed: 12023286
Nat Rev Drug Discov. 2016 Aug;15(8):533-50
pubmed: 27050677
Biochemistry. 2016 May 10;55(18):2601-12
pubmed: 27089101
Drug Discov Today. 2014 Apr;19(4):388-99
pubmed: 24157402