Macrocyclization as a Source of Desired Polypharmacology. Discovery of Triple PI3K/mTOR/PIM Inhibitors.


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:
11 Nov 2021
Historique:
received: 28 07 2021
accepted: 28 10 2021
entrez: 19 11 2021
pubmed: 20 11 2021
medline: 20 11 2021
Statut: epublish

Résumé

The PI3K/AKT/mTOR and PIM kinase pathways contribute to the development of several hallmarks of cancer. Cotargeting of these pathways has exhibited promising synergistic therapeutic effects in liquid and solid tumor types. To identify molecules with combined activities, we cross-screened our collection of PI3K/(±mTOR) macrocycles (MCXs) and identified the MCX thieno[3,2-

Identifiants

pubmed: 34795869
doi: 10.1021/acsmedchemlett.1c00412
pmc: PMC8591745
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1794-1801

Informations de copyright

© 2021 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

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Auteurs

Sonia Martínez-González (S)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Rosa M Alvarez (RM)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

José I Martín (JI)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Ana Belén García (AB)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Concepción Riesco-Fagundo (C)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Carmen Varela (C)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Antonio Rodríguez Hergueta (A)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Esther González Cantalapiedra (E)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

M I Albarrán (MI)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Elena Gómez-Casero (E)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Antonio Cebriá (A)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Enara Aguirre (E)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Nuria Ajenjo (N)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

David Cebrián (D)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Bruno Di Geronimo (B)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Darren Cunningham (D)

Inflection Biosciences Ltd., Suite 15, Anglesea 419 House, Carysfort Avenue Blackrock, Dublin A94 VC59, Ireland.

Michael O'Neill (M)

Inflection Biosciences Ltd., Suite 15, Anglesea 419 House, Carysfort Avenue Blackrock, Dublin A94 VC59, Ireland.

Harish P G Dave (HPG)

AUM Biosciences, 24-428 16A, 10 Anson Road, International Plaza, Singapore 429 079903.

Carmen Blanco-Aparicio (C)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Joaquín Pastor (J)

Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Classifications MeSH