Establishing Drug Discovery and Identification of Hit Series for the Anti-apoptotic Proteins, Bcl-2 and Mcl-1.
Journal
ACS omega
ISSN: 2470-1343
Titre abrégé: ACS Omega
Pays: United States
ID NLM: 101691658
Informations de publication
Date de publication:
31 May 2019
31 May 2019
Historique:
received:
05
03
2019
accepted:
08
03
2019
entrez:
29
8
2019
pubmed:
29
8
2019
medline:
29
8
2019
Statut:
epublish
Résumé
We describe our work to establish structure- and fragment-based drug discovery to identify small molecules that inhibit the anti-apoptotic activity of the proteins Mcl-1 and Bcl-2. This identified hit series of compounds, some of which were subsequently optimized to clinical candidates in trials for treating various cancers. Many protein constructs were designed to identify protein with suitable properties for different biophysical assays and structural methods. Fragment screening using ligand-observed NMR experiments identified several series of compounds for each protein. The series were assessed for their potential for subsequent optimization using
Identifiants
pubmed: 31459977
doi: 10.1021/acsomega.9b00611
pmc: PMC6648477
doi:
Types de publication
Journal Article
Langues
eng
Pagination
8892-8906Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
Références
Annu Rev Biophys Biomol Struct. 1999;28:155-79
pubmed: 10410799
Acta Crystallogr D Biol Crystallogr. 1999 Oct;55(Pt 10):1718-25
pubmed: 10531521
J Med Chem. 2000 Sep 7;43(18):3443-7
pubmed: 10978192
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3012-7
pubmed: 11248023
J Biomol NMR. 2001 Dec;21(4):349-59
pubmed: 11824754
J Med Chem. 2004 Mar 25;47(7):1750-9
pubmed: 15027866
Acta Crystallogr D Biol Crystallogr. 2004 Aug;60(Pt 8):1355-63
pubmed: 15272157
Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
pubmed: 15299926
Anal Biochem. 2004 Sep 15;332(2):261-73
pubmed: 15325294
J Chem Inf Comput Sci. 2004 Nov-Dec;44(6):2157-66
pubmed: 15554686
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Mol Cell. 2005 Feb 4;17(3):393-403
pubmed: 15694340
J Med Chem. 2005 Apr 7;48(7):2518-25
pubmed: 15801841
Proteins. 2005 Jun 1;59(4):687-96
pubmed: 15815974
Nature. 2005 Jun 2;435(7042):677-81
pubmed: 15902208
J Med Chem. 2006 Jan 26;49(2):534-53
pubmed: 16420040
Nat Biotechnol. 2007 Jan;25(1):71-5
pubmed: 17211405
Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6217-22
pubmed: 17389404
Cell Death Differ. 2007 Sep;14(9):1711-3
pubmed: 17572662
Nature. 2007 Dec 13;450(7172):1001-9
pubmed: 18075579
Curr Protoc Bioinformatics. 2007 Jun;Chapter 8:Unit 8.12
pubmed: 18428795
Cancer Res. 2008 May 1;68(9):3421-8
pubmed: 18451170
Bioorg Med Chem Lett. 2009 Jan 1;19(1):230-3
pubmed: 19027294
J Comput Aided Mol Des. 2009 Aug;23(8):603-20
pubmed: 19495994
J Med Chem. 2009 Aug 13;52(15):4794-809
pubmed: 19610616
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):22-5
pubmed: 20057045
Protein Sci. 2010 Mar;19(3):507-19
pubmed: 20066663
Anal Chem. 2011 Mar 1;83(5):1800-7
pubmed: 21314134
Drug Discov Today. 2011 Apr;16(7-8):284-7
pubmed: 21315179
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42
pubmed: 21460441
Nat Med. 2013 Feb;19(2):202-8
pubmed: 23291630
J Comput Aided Mol Des. 2013 Mar;27(3):221-34
pubmed: 23579614
Nat Rev Cancer. 2013 Jul;13(7):455-65
pubmed: 23783119
J Med Chem. 2015 Mar 12;58(5):2180-94
pubmed: 25679114
PLoS One. 2015 Apr 24;10(4):e0125010
pubmed: 25909780
J Med Chem. 2016 Mar 10;59(5):2054-66
pubmed: 26878343
J Med Chem. 2017 Feb 9;60(3):821-838
pubmed: 27749061
Nature. 2016 Oct 27;538(7626):477-482
pubmed: 27760111
ACS Med Chem Lett. 2016 Dec 27;8(2):239-244
pubmed: 28197319
Bioorg Med Chem. 2017 Jun 15;25(12):3087-3092
pubmed: 28428041
J Med Chem. 2017 Jun 22;60(12):4923-4931
pubmed: 28537726
Angew Chem Int Ed Engl. 1999 Jun 14;38(12):1784-1788
pubmed: 29711196
Oncotarget. 2018 Apr 13;9(28):20075-20088
pubmed: 29732004
J Med Chem. 2019 Aug 8;62(15):6913-6924
pubmed: 31339316
Nature. 1996 May 23;381(6580):335-41
pubmed: 8692274