IOA-244 is a Non-ATP-competitive, Highly Selective, Tolerable PI3K Delta Inhibitor That Targets Solid Tumors and Breaks Immune Tolerance.


Journal

Cancer research communications
ISSN: 2767-9764
Titre abrégé: Cancer Res Commun
Pays: United States
ID NLM: 9918281580506676

Informations de publication

Date de publication:
04 2023
Historique:
received: 22 11 2022
revised: 21 12 2022
accepted: 14 03 2023
medline: 18 4 2023
entrez: 17 4 2023
pubmed: 18 4 2023
Statut: epublish

Résumé

PI3K delta (PI3Kδ) inhibitors are used to treat lymphomas but safety concerns and limited target selectivity curbed their clinical usefulness. PI3Kδ inhibition in solid tumors has recently emerged as a potential novel anticancer therapy through the modulation of T-cell responses and direct antitumor activity. Here we report the exploration of IOA-244/MSC2360844, a first-in-class non-ATP-competitive PI3Kδ inhibitor, for the treatment of solid tumors. We confirm IOA-244's selectivity as tested against a large set of kinases, enzymes, and receptors. IOA-244 inhibits the IOA-244 is a first-in-class non-ATP-competitive, PI3Kδ inhibitor with direct antitumor

Identifiants

pubmed: 37066023
doi: 10.1158/2767-9764.CRC-22-0477
pii: CRC-22-0477
pmc: PMC10103717
doi:

Substances chimiques

Phosphatidylinositol 3-Kinases EC 2.7.1.-
Phosphoinositide-3 Kinase Inhibitors 0

Types de publication

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

Langues

eng

Pagination

576-591

Informations de copyright

© 2023 The Authors; Published by the American Association for Cancer Research.

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Auteurs

Zoë Johnson (Z)

iOnctura SA, Geneva, Switzerland.

Chiara Tarantelli (C)

Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.

Elisa Civanelli (E)

Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.

Luciano Cascione (L)

Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.
SIB, Swiss Institute of Bioinformatics, Lausanne, Switzerland.

Filippo Spriano (F)

Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.

Amy Fraser (A)

Cancer Research Horizons, Jonas Webb Building, Cambridge, United Kingdom.

Pritom Shah (P)

Cancer Research Horizons, Jonas Webb Building, Cambridge, United Kingdom.

Tyzoon Nomanbhoy (T)

ActivX Biosciences, Inc., La Jolla, California.

Sara Napoli (S)

Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.

Andrea Rinaldi (A)

Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.

Michael Lahn (M)

iOnctura SA, Geneva, Switzerland.

Dominique Perrin (D)

Merck Healthcare KGaA, Darmstadt, Germany.

Mathias Wenes (M)

Brain Tumor and Immune Cell Engineering Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Center for Translational Research in Onco-Hematology, University of Geneva, Geneva, Switzerland.
Swiss Cancer Center Leman, Geneva and Lausanne, Switzerland.

Denis Migliorini (D)

Brain Tumor and Immune Cell Engineering Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Center for Translational Research in Onco-Hematology, University of Geneva, Geneva, Switzerland.
Swiss Cancer Center Leman, Geneva and Lausanne, Switzerland.
Department of Oncology, Geneva University Hospitals (HUG), Geneva, Switzerland.

Francesco Bertoni (F)

Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.
Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.

Lars van der Veen (L)

iOnctura SA, Geneva, Switzerland.

Giusy Di Conza (G)

iOnctura SA, Geneva, Switzerland.

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Classifications MeSH