Achieving
Animals
Benzimidazoles
/ administration & dosage
Cell Line, Tumor
Drug Delivery Systems
/ methods
Drug Discovery
/ methods
Female
Humans
Male
Mice
Mice, Inbred BALB C
Mice, SCID
Microsomes, Liver
/ drug effects
Protein Structure, Tertiary
Proto-Oncogene Proteins c-bcl-6
/ antagonists & inhibitors
Rats
Rats, Sprague-Dawley
Xenograft Model Antitumor Assays
/ methods
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
23 04 2020
23 04 2020
Historique:
pubmed:
11
4
2020
medline:
25
9
2020
entrez:
11
4
2020
Statut:
ppublish
Résumé
Deregulation of the transcriptional repressor BCL6 enables tumorigenesis of germinal center B-cells, and hence BCL6 has been proposed as a therapeutic target for the treatment of diffuse large B-cell lymphoma (DLBCL). Herein we report the discovery of a series of benzimidazolone inhibitors of the protein-protein interaction between BCL6 and its co-repressors. A subset of these inhibitors were found to cause rapid degradation of BCL6, and optimization of pharmacokinetic properties led to the discovery of 5-((5-chloro-2-((3
Identifiants
pubmed: 32275432
doi: 10.1021/acs.jmedchem.9b02076
pmc: PMC7184563
doi:
Substances chimiques
BCL6 protein, human
0
Benzimidazoles
0
Proto-Oncogene Proteins c-bcl-6
0
benzimidazolone
20662-53-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4047-4068Subventions
Organisme : Cancer Research UK
ID : C309/A11566
Pays : United Kingdom
Références
Nat Med. 2004 Dec;10(12):1329-35
pubmed: 15531890
J Med Chem. 2010 Jul 22;53(14):5061-84
pubmed: 20345171
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Cancer Cell. 2010 Apr 13;17(4):400-11
pubmed: 20385364
Cell Res. 2016 Apr;26(4):484-98
pubmed: 27002218
Biochem J. 2017 Mar 15;474(7):1127-1147
pubmed: 28298557
Angew Chem Int Ed Engl. 2015 Aug 10;54(33):9659-62
pubmed: 26083457
Pathol Biol (Paris). 2007 Feb;55(1):73-83
pubmed: 16815642
Cell. 2000 Jan 7;100(1):57-70
pubmed: 10647931
J Clin Invest. 2016 Sep 1;126(9):3351-62
pubmed: 27482887
Bioorg Med Chem. 2017 Sep 1;25(17):4876-4886
pubmed: 28760529
Nat Rev Drug Discov. 2017 Feb;16(2):101-114
pubmed: 27885283
Drug Discov Today. 2016 Jul;21(7):1139-46
pubmed: 27210724
Drug Discov Today. 2010 Aug;15(15-16):648-55
pubmed: 20570751
Immunol Rev. 2012 May;247(1):172-83
pubmed: 22500840
ACS Chem Biol. 2018 Nov 16;13(11):3131-3141
pubmed: 30335946
Cell Rep. 2017 Sep 19;20(12):2860-2875
pubmed: 28930682
J Med Chem. 2017 May 25;60(10):4386-4402
pubmed: 28485934
Expert Opin Drug Discov. 2019 Mar;14(3):221-230
pubmed: 30675823
Nat Chem Biol. 2015 Aug;11(8):611-7
pubmed: 26075522
J Med Chem. 2017 May 25;60(10):4358-4368
pubmed: 28471657
Blood. 2009 Apr 9;113(15):3397-405
pubmed: 18927431
Oncotarget. 2016 Nov 22;7(47):77444-77456
pubmed: 27764808
Mol Cell. 2008 Feb 15;29(3):384-91
pubmed: 18280243
Trends Mol Med. 2014 Jun;20(6):343-52
pubmed: 24698494