New Dual CK2/HDAC1 Inhibitors with Nanomolar Inhibitory Activity against Both Enzymes.


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:
14 May 2020
Historique:
received: 30 11 2019
accepted: 07 04 2020
entrez: 22 5 2020
pubmed: 22 5 2020
medline: 22 5 2020
Statut: epublish

Résumé

Four potent CK2 inhibitors derived from CX-4945 are described. They also provided nanomolar activity against HDAC1, therefore having promising utility as dual-target agents for cancer. The linker length between the hydroxamic acid and the CX-4945 scaffold plays an important role in dictating balanced activity against the targeted enzymes. The seven-carbon linker (compound

Identifiants

pubmed: 32435375
doi: 10.1021/acsmedchemlett.9b00561
pmc: PMC7236037
doi:

Types de publication

Journal Article

Langues

eng

Pagination

713-719

Informations de copyright

Copyright © 2020 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

Références

Cell Mol Life Sci. 2009 Jun;66(11-12):1858-67
pubmed: 19387548
Cancer Res. 2001 Dec 1;61(23):8492-7
pubmed: 11731433
J Biol Chem. 2013 Jun 7;288(23):16518-28
pubmed: 23612983
Biochemistry. 2011 Oct 4;50(39):8478-88
pubmed: 21870818
Structure. 2004 Jul;12(7):1325-34
pubmed: 15242608
Curr Cancer Drug Targets. 2018;18(1):39-56
pubmed: 28176653
Hepatology. 2011 Jan;53(1):148-59
pubmed: 21254166
Nat Commun. 2018 Aug 28;9(1):3490
pubmed: 30154431
Nat Rev Clin Oncol. 2017 Jan;14(1):57-66
pubmed: 27377132
Molecules. 2020 Mar 25;25(7):
pubmed: 32218358
Front Oncol. 2018 Mar 29;8:92
pubmed: 29651407
FEBS J. 2014 Feb;281(3):851-61
pubmed: 24616922
Biochem Pharmacol. 2014 Aug 1;90(3):320-30
pubmed: 24915421
BMC Pharmacol Toxicol. 2013 Jul 11;14:36
pubmed: 23845105
Semin Oncol. 2018 Jan;45(1-2):58-67
pubmed: 30318085
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2995-3000
pubmed: 11867742
Cold Spring Harb Perspect Med. 2016 Oct 3;6(10):
pubmed: 27599530
Cancer Res. 2010 Dec 15;70(24):10288-98
pubmed: 21159648
Int J Cancer. 2008 Jan 15;122(2):333-41
pubmed: 17935135
Med Res Rev. 2018 Sep;38(6):2058-2109
pubmed: 29733427
J Med Chem. 2019 Oct 24;62(20):8881-8914
pubmed: 31082225
Amino Acids. 2018 May;50(5):609-619
pubmed: 29307075
Curr Opin Chem Biol. 2019 Jun;50:89-100
pubmed: 30986654
Oncol Lett. 2015 Feb;9(2):515-521
pubmed: 25624882
J Med Chem. 2011 Jan 27;54(2):635-54
pubmed: 21174434
Eur J Med Chem. 2019 Nov 1;181:111581
pubmed: 31400711
Mol Cell Biochem. 2017 Nov;435(1-2):193-196
pubmed: 28501934
J Biol Chem. 2008 Apr 25;283(17):11355-63
pubmed: 18285338
J Inorg Biochem. 2016 Jul;160:156-65
pubmed: 26818702
J Med Chem. 2019 Apr 11;62(7):3171-3183
pubmed: 30418766
J Biol Chem. 2013 Sep 13;288(37):26926-43
pubmed: 23897821
Neuropharmacology. 2012 Sep;63(3):368-73
pubmed: 22548713
J Biol Chem. 2016 Feb 12;291(7):3158-72
pubmed: 26663086
Cancer Res. 2000 Sep 15;60(18):5165-70
pubmed: 11016644
J Biol Chem. 2016 Feb 19;291(8):4004-18
pubmed: 26655717

Auteurs

Loganathan Rangasamy (L)

Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28925 Alcorcón, Madrid, Spain.

Irene Ortín (I)

Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28925 Alcorcón, Madrid, Spain.

José María Zapico (JM)

Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28925 Alcorcón, Madrid, Spain.

Claire Coderch (C)

Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28925 Alcorcón, Madrid, Spain.

Ana Ramos (A)

Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28925 Alcorcón, Madrid, Spain.

Beatriz de Pascual-Teresa (B)

Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28925 Alcorcón, Madrid, Spain.

Classifications MeSH