Computer-aided identification, synthesis, and biological evaluation of DNA polymerase η inhibitors for the treatment of cancer.


Journal

European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510

Informations de publication

Date de publication:
15 Feb 2023
Historique:
received: 22 08 2022
revised: 20 12 2022
accepted: 20 12 2022
pubmed: 10 1 2023
medline: 1 2 2023
entrez: 9 1 2023
Statut: ppublish

Résumé

In cancer cells, Pol η allows DNA replication and cell proliferation even in the presence of chemotherapeutic drug-induced damages, like in the case of platinum-containing drugs. Inhibition of Pol η thus represents a promising strategy to overcome drug resistance and preserve the effectiveness of chemotherapeutic drugs. Here, we report the discovery of a novel class of Pol ƞ inhibitors, with 35 active close analogs. Compound 21 (ARN24964) stands out as the best inhibitor, with an IC

Identifiants

pubmed: 36621139
pii: S0223-5234(22)00946-1
doi: 10.1016/j.ejmech.2022.115044
pii:
doi:

Substances chimiques

Rad30 protein EC 2.7.7.7
Platinum 49DFR088MY

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

115044

Informations de copyright

Copyright © 2023 Elsevier Masson SAS. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marco De Vivo reports financial support was provided by Italian Association for Cancer Research. Marco De Vivo reports a relationship with Italian Institute of Technology that includes: funding grants. Marco De Vivo has patent #patent application IT 102022000007988. pending to Italian Institute of Technology. Nicoletta Brindani has patent #patent application IT 102022000007988. pending to Italian Institute of Technology. Federico Munafo’ has patent #patent application IT 102022000007988. pending to Italian Institute of Technology. Michela Nigro has patent #patent application IT 102022000007988. pending to Italian Institute of Technology. None.

Auteurs

Federico Munafò (F)

Molecular Modeling and Drug Discovery Lab, Istituto Italiano di Tecnologia, via Morego 30, 16163, Genova, Italy.

Michela Nigro (M)

Molecular Modeling and Drug Discovery Lab, Istituto Italiano di Tecnologia, via Morego 30, 16163, Genova, Italy.

Nicoletta Brindani (N)

Molecular Modeling and Drug Discovery Lab, Istituto Italiano di Tecnologia, via Morego 30, 16163, Genova, Italy.

Jacopo Manigrasso (J)

Molecular Modeling and Drug Discovery Lab, Istituto Italiano di Tecnologia, via Morego 30, 16163, Genova, Italy.

Inacrist Geronimo (I)

Molecular Modeling and Drug Discovery Lab, Istituto Italiano di Tecnologia, via Morego 30, 16163, Genova, Italy.

Giuliana Ottonello (G)

Analytical Chemistry Facility, Istituto Italiano di Tecnologia, via Morego, 30, 16163, Genoa, Italy.

Andrea Armirotti (A)

Analytical Chemistry Facility, Istituto Italiano di Tecnologia, via Morego, 30, 16163, Genoa, Italy.

Marco De Vivo (M)

Molecular Modeling and Drug Discovery Lab, Istituto Italiano di Tecnologia, via Morego 30, 16163, Genova, Italy. Electronic address: marco.devivo@iit.it.

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Classifications MeSH