Targeting phosphatidylinositol 3-kinase gamma (PI3Kγ): Discovery and development of its selective inhibitors.
IPI-549
PI3Kγ
isoform selective inhibitors
molecular modeling
phosphoinositide 3-kinase gamma
structure-activity relationship (SAR)
Journal
Medicinal research reviews
ISSN: 1098-1128
Titre abrégé: Med Res Rev
Pays: United States
ID NLM: 8103150
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
13
10
2020
received:
12
01
2020
accepted:
29
11
2020
pubmed:
11
12
2020
medline:
29
10
2021
entrez:
10
12
2020
Statut:
ppublish
Résumé
Phosphatidylinositol 3-kinase gamma (PI3Kγ) has been regarded as a promising drug target for the treatment of advanced solid tumors, leukemia, lymphoma, and inflammatory and autoimmune diseases. However, the high level of structural conservation among the members of the PI3K family and the diverse physiological roles of Class I PI3K isoforms (α, β, δ, and γ) highlight the importance of isoform selectivity in the development of PI3Kγ inhibitors. In this review, we provide an overview of the structural features of PI3Kγ that influence γ-isoform selectivity and discuss the structure-selectivity-activity relationship of existing clinical PI3Kγ inhibitors. Additionally, we summarize the experimental and computational techniques utilized to identify PI3Kγ inhibitors. The insights gained so far could be used to overcome the main challenges in development and accelerate the discovery of PI3Kγ-selective inhibitors.
Substances chimiques
Phosphoinositide-3 Kinase Inhibitors
0
Class Ib Phosphatidylinositol 3-Kinase
EC 2.7.1.137
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1599-1621Informations de copyright
© 2020 Wiley Periodicals LLC.
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