Design and Synthesis of Novel Epigenetic Inhibitors Targeting Histone Deacetylases, DNA Methyltransferase 1, and Lysine Methyltransferase G9a with


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:
25 03 2021
Historique:
pubmed: 5 3 2021
medline: 5 6 2021
entrez: 4 3 2021
Statut: ppublish

Résumé

Concomitant inhibition of key epigenetic pathways involved in silencing tumor suppressor genes has been recognized as a promising strategy for cancer therapy. Herein, we report a first-in-class series of quinoline-based analogues that simultaneously inhibit histone deacetylases (from a low nanomolar range) and DNA methyltransferase-1 (from a mid-nanomolar range, IC

Identifiants

pubmed: 33661013
doi: 10.1021/acs.jmedchem.0c02255
doi:

Substances chimiques

Antineoplastic Agents 0
Enzyme Inhibitors 0
Histocompatibility Antigens 0
Histone Deacetylase Inhibitors 0
DNA (Cytosine-5-)-Methyltransferase 1 EC 2.1.1.37
DNMT1 protein, human EC 2.1.1.37
EHMT2 protein, human EC 2.1.1.43
Histone-Lysine N-Methyltransferase EC 2.1.1.43
Histone Deacetylases EC 3.5.1.98

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3392-3426

Auteurs

Obdulia Rabal (O)

Small Molecule Discovery Platform, Molecular Therapeutics Program, Center for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII 55, E-31008 Pamplona, Spain.

Edurne San José-Enériz (E)

Area de Hemato-Oncología, IDISNA, CIBERONC, Center for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII 55, E-31008 Pamplona, Spain.

Xabier Agirre (X)

Area de Hemato-Oncología, IDISNA, CIBERONC, Center for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII 55, E-31008 Pamplona, Spain.

Juan Antonio Sánchez-Arias (JA)

Small Molecule Discovery Platform, Molecular Therapeutics Program, Center for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII 55, E-31008 Pamplona, Spain.

Irene de Miguel (I)

Small Molecule Discovery Platform, Molecular Therapeutics Program, Center for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII 55, E-31008 Pamplona, Spain.

Raquel Ordoñez (R)

Area de Hemato-Oncología, IDISNA, CIBERONC, Center for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII 55, E-31008 Pamplona, Spain.

Leire Garate (L)

Area de Hemato-Oncología, IDISNA, CIBERONC, Center for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII 55, E-31008 Pamplona, Spain.

Estíbaliz Miranda (E)

Area de Hemato-Oncología, IDISNA, CIBERONC, Center for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII 55, E-31008 Pamplona, Spain.

Elena Sáez (E)

Small Molecule Discovery Platform, Molecular Therapeutics Program, Center for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII 55, E-31008 Pamplona, Spain.

Amaia Vilas-Zornoza (A)

Area de Hemato-Oncología, IDISNA, CIBERONC, Center for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII 55, E-31008 Pamplona, Spain.

Antonio Pineda-Lucena (A)

Small Molecule Discovery Platform, Molecular Therapeutics Program, Center for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII 55, E-31008 Pamplona, Spain.

Ander Estella (A)

Small Molecule Discovery Platform, Molecular Therapeutics Program, Center for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII 55, E-31008 Pamplona, Spain.

Feifei Zhang (F)

WuXi Apptec (Tianjin) Company Ltd., TEDA, No. 168 Nanhai Road, 10th Avenue, 300456 Tianjin, PR China.

Wei Wu (W)

WuXi Apptec (Tianjin) Company Ltd., TEDA, No. 168 Nanhai Road, 10th Avenue, 300456 Tianjin, PR China.

Musheng Xu (M)

WuXi Apptec (Tianjin) Company Ltd., TEDA, No. 168 Nanhai Road, 10th Avenue, 300456 Tianjin, PR China.

Felipe Prosper (F)

Area de Hemato-Oncología, IDISNA, CIBERONC, Center for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII 55, E-31008 Pamplona, Spain.
Departmento de Hematología, Clínica Universidad de Navarra, University of Navarra, Avenida Pio XII 36, E-31008 Pamplona, Spain.

Julen Oyarzabal (J)

Small Molecule Discovery Platform, Molecular Therapeutics Program, Center for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII 55, E-31008 Pamplona, Spain.

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Classifications MeSH