Aminopyrazole based CDK9 PROTAC sensitizes pancreatic cancer cells to venetoclax.
Antineoplastic Agents
/ pharmacology
Bridged Bicyclo Compounds, Heterocyclic
/ pharmacology
Cell Proliferation
/ drug effects
Cyclin-Dependent Kinase 9
/ antagonists & inhibitors
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Pancreatic Neoplasms
/ drug therapy
Protein Kinase Inhibitors
/ chemistry
Proteolysis
/ drug effects
Pyrazoles
/ chemistry
Structure-Activity Relationship
Sulfonamides
/ pharmacology
Aminopyrazole
CDK
Cancer
PROTAC
Venetoclax
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
01 07 2021
01 07 2021
Historique:
received:
11
02
2021
revised:
15
04
2021
accepted:
19
04
2021
pubmed:
26
4
2021
medline:
3
11
2021
entrez:
25
4
2021
Statut:
ppublish
Résumé
Cyclin-dependent kinase 9 (CDK9) is a member of the cyclin-dependent kinase (CDK) family which is involved in transcriptional regulation of several genes, including the oncogene Myc, and is a validated target for pancreatic cancer. Here we report the development of an aminopyrazole based proteolysis targeting chimera (PROTAC 2) that selectively degrades CDK9 (DC
Identifiants
pubmed: 33895280
pii: S0960-894X(21)00287-0
doi: 10.1016/j.bmcl.2021.128061
pmc: PMC8187316
mid: NIHMS1697804
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Bridged Bicyclo Compounds, Heterocyclic
0
Protein Kinase Inhibitors
0
Pyrazoles
0
Sulfonamides
0
CDK9 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 9
EC 2.7.11.22
venetoclax
N54AIC43PW
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
128061Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM121316
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA036727
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA197999
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA251151
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
Références
J Med Chem. 2004 Jun 17;47(13):3367-80
pubmed: 15189033
Leuk Res. 2011 Jun;35(6):821-30
pubmed: 21216463
Chem Commun (Camb). 2017 Jul 4;53(54):7577-7580
pubmed: 28636052
Cell Cycle. 2011 Jan 1;10(1):28-32
pubmed: 21200140
Bioorg Med Chem Lett. 2018 Dec 15;28(23-24):3736-3740
pubmed: 30343954
Bioorg Med Chem Lett. 2019 Jun 1;29(11):1375-1379
pubmed: 30935795
Oncogene. 1999 Aug 12;18(32):4598-605
pubmed: 10467404
Cancer Res. 2008 May 1;68(9):3421-8
pubmed: 18451170
Curr Med Chem. 2017;24(40):4488-4514
pubmed: 28901269
J Biol Chem. 2010 May 14;285(20):15016-15026
pubmed: 20223826
Cancer Cell. 2006 Nov;10(5):375-88
pubmed: 17097560
Mol Pharmacol. 2019 Oct;96(4):419-429
pubmed: 31467029
Clin Cancer Res. 2011 Sep 15;17(18):5973-81
pubmed: 21821698
EMBO Rep. 2010 Nov;11(11):876-82
pubmed: 20930849
Science. 2015 Jun 19;348(6241):1376-81
pubmed: 25999370
Nat Biotechnol. 2011 Oct 30;29(11):1039-45
pubmed: 22037377
Cancers (Basel). 2015 Jan 23;7(1):179-237
pubmed: 25625291
Cancer Res. 2005 Jun 15;65(12):5399-407
pubmed: 15958589
J Med Chem. 2016 Oct 13;59(19):8667-8684
pubmed: 27171036
J Med Chem. 2019 Aug 22;62(16):7575-7582
pubmed: 31330105
BMC Cancer. 2012 Nov 21;12:541
pubmed: 23171055
Sci Signal. 2019 Jul 16;12(590):
pubmed: 31311847
Chembiochem. 2007 Nov 23;8(17):2058-62
pubmed: 17907127
Oncotarget. 2017 Dec 28;9(4):5216-5232
pubmed: 29435174
Bioorg Med Chem. 2012 Apr 1;20(7):2227-34
pubmed: 22386982
Chem Biol Drug Des. 2020 Aug;96(2):773-784
pubmed: 32237047
Open Biol. 2018 Sep;8(9):
pubmed: 30185601
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8554-9
pubmed: 11438690
Nat Chem Biol. 2018 Feb;14(2):163-170
pubmed: 29251720
ACS Chem Biol. 2015 Aug 21;10(8):1770-7
pubmed: 26035625
Bioorg Chem. 2018 Dec;81:373-381
pubmed: 30196207
ACS Chem Biol. 2018 May 18;13(5):1148-1152
pubmed: 29608269
Genes Dev. 2014 Aug 15;28(16):1800-14
pubmed: 25128497
Cell Chem Biol. 2019 Feb 21;26(2):300-306.e9
pubmed: 30595531
Eur J Med Chem. 2021 Feb 5;211:113091
pubmed: 33338869
Chem Biol. 2015 Jun 18;22(6):755-63
pubmed: 26051217