Selective and Potent CDK8/19 Inhibitors Enhance NK-Cell Activity and Promote Tumor Surveillance.


Journal

Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535

Informations de publication

Date de publication:
04 2020
Historique:
received: 12 08 2019
revised: 18 12 2019
accepted: 28 01 2020
pubmed: 7 2 2020
medline: 7 4 2021
entrez: 7 2 2020
Statut: ppublish

Résumé

Natural killer (NK) cells play a pivotal role in controlling cancer. Multiple extracellular receptors and internal signaling nodes tightly regulate NK activation. Cyclin-dependent kinases of the mediator complex (CDK8 and CDK19) were described as a signaling intermediates in NK cells. Here, we report for the first time the development and use of CDK8/19 inhibitors to suppress phosphorylation of STAT1

Identifiants

pubmed: 32024684
pii: 1535-7163.MCT-19-0789
doi: 10.1158/1535-7163.MCT-19-0789
pmc: PMC7661742
mid: NIHMS1556854
doi:

Substances chimiques

Protein Kinase Inhibitors 0
STAT1 Transcription Factor 0
STAT1 protein, human 0
CDK19 protein, human EC 2.7.11.22
CDK8 protein, human EC 2.7.11.22
Cyclin-Dependent Kinase 8 EC 2.7.11.22
Cyclin-Dependent Kinases EC 2.7.11.22

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1018-1030

Subventions

Organisme : NCI NIH HHS
ID : F99 CA245813
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016058
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA159296
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA197844
Pays : United States

Informations de copyright

©2020 American Association for Cancer Research.

Références

J Med Chem. 2016 Feb 11;59(3):1078-101
pubmed: 26796641
Nat Chem Biol. 2015 Dec;11(12):973-980
pubmed: 26502155
Nature. 2015 Oct 8;526(7572):273-276
pubmed: 26416749
Proc Natl Acad Sci U S A. 2013 May 14;110(20):8081-6
pubmed: 23630251
Biochim Biophys Acta. 2015 Oct;1854(10 Pt B):1617-29
pubmed: 26006748
Nature. 2008 Sep 25;455(7212):547-51
pubmed: 18794900
Cancer Cell. 2018 Apr 9;33(4):581-598
pubmed: 29634946
Leukemia. 2017 Oct;31(10):2172-2180
pubmed: 28096534
J Immunol. 2000 Oct 1;165(7):3571-7
pubmed: 11034357
Blood. 2016 Jun 9;127(23):2879-89
pubmed: 27013443
Semin Immunol. 2014 Apr;26(2):138-44
pubmed: 24629893
Lancet. 2000 Nov 25;356(9244):1795-9
pubmed: 11117911
J Clin Invest. 2018 Oct 1;128(10):4654-4668
pubmed: 30198904
J Clin Oncol. 2009 Mar 1;27(7):1122-9
pubmed: 19164213
Nat Commun. 2014 Oct 30;5:5108
pubmed: 25355530
Nat Rev Drug Discov. 2015 Jul;14(7):487-98
pubmed: 26000725
Oncotarget. 2017 May 16;8(20):33779-33795
pubmed: 28422713
Apoptosis. 2017 Jul;22(7):898-919
pubmed: 28424988
Science. 2011 Jan 7;331(6013):44-9
pubmed: 21212348
J Immunol. 1987 Jun 15;138(12):4539-44
pubmed: 3584981
Haematologica. 2015 May;100(5):643-52
pubmed: 25682594
Oncotarget. 2017 Feb 21;8(8):12558-12575
pubmed: 28147342
J Clin Invest. 2018 Aug 1;128(8):3209-3218
pubmed: 30067248
Leuk Lymphoma. 2014 Mar;55(3):645-51
pubmed: 23697877
Oncoimmunology. 2014 Apr 29;3:e28541
pubmed: 25050221
Immunol Rev. 2006 Dec;214:73-91
pubmed: 17100877
Int J Cancer. 2004 Mar;109(1):85-94
pubmed: 14735472
Genes Cells. 2011 Dec;16(12):1208-18
pubmed: 22117896
N Engl J Med. 2012 Jun 28;366(26):2443-54
pubmed: 22658127
Oncoimmunology. 2016 May 19;5(9):e1186314
pubmed: 27757297
J Med Chem. 2018 Jun 28;61(12):5073-5092
pubmed: 29266937
J Exp Med. 2000 Oct 2;192(7):1027-34
pubmed: 11015443
Cell Rep. 2013 Aug 15;4(3):437-44
pubmed: 23933255
Int J Clin Lab Res. 1997;27(1):48-54
pubmed: 9144027
J Clin Oncol. 2008 Apr 10;26(11):1789-96
pubmed: 18347005
Blood. 2008 Aug 1;112(3):461-9
pubmed: 18650461
Elife. 2016 Dec 09;5:
pubmed: 27935476
Adv Immunol. 2009;101:27-79
pubmed: 19231592
Oncotarget. 2018 Jan 3;9(11):9706-9713
pubmed: 29515764
Cancer Immunol Res. 2018 Apr;6(4):458-466
pubmed: 29386186
J Pharmacol Exp Ther. 2015 Mar;352(3):579-89
pubmed: 25576074
Immunity. 2013 Feb 21;38(2):250-62
pubmed: 23352233
Nat Commun. 2017 Feb 15;8:
pubmed: 28198370
Trends Immunol. 2009 Apr;30(4):143-9
pubmed: 19282243
Clin Cancer Res. 2015 Sep 15;21(18):4055-61
pubmed: 25999435
J Biomol Screen. 2011 Mar;16(3):370-7
pubmed: 21335598
Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13799-804
pubmed: 22869755
Nat Rev Immunol. 2018 Mar;18(3):153-167
pubmed: 28990585
Cancer Immunol Res. 2018 Jan;6(1):25-35
pubmed: 29187357

Auteurs

Marco H Hofmann (MH)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria. marco.hofmann@boehringer-ingelheim.com.

Rajeswaran Mani (R)

Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.

Harald Engelhardt (H)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Maria A Impagnatiello (MA)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Sebastian Carotta (S)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Marc Kerenyi (M)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Seila Lorenzo-Herrero (S)

Department of Functional Biology, Universidad de Oviedo, Instituto de Investigación Biosanitaria del Principado de Asturias (IISPA), IUOPA, Oviedo, Spain.

Jark Böttcher (J)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Dirk Scharn (D)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Heribert Arnhof (H)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Andreas Zoephel (A)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Renate Schnitzer (R)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Thomas Gerstberger (T)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Michael P Sanderson (MP)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Girish Rajgolikar (G)

Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.

Swagata Goswami (S)

Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.

Sumithira Vasu (S)

Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.

Peter Ettmayer (P)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Segundo Gonzalez (S)

Department of Functional Biology, Universidad de Oviedo, Instituto de Investigación Biosanitaria del Principado de Asturias (IISPA), IUOPA, Oviedo, Spain.

Mark Pearson (M)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Darryl B McConnell (DB)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Norbert Kraut (N)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Natarajan Muthusamy (N)

Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.

Jürgen Moll (J)

Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH