Open AccessTargeting Phosphoinositide 3-Kinase – Five Decades of Chemical Space Exploration
Author(s) -
Chiara Borsari,
Matthias P. Wymann
Publication year - 2021
Publication title -
chimia
Language(s) - English
Resource type - Journals
eISSN - 2673-2424
pISSN - 0009-4293
DOI - 10.2533/chimia.2021.1037
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , drug discovery , kinase , phosphoinositide 3 kinase , computational biology , biology , signal transduction , bioinformatics , cancer research , microbiology and biotechnology
Phosphoinositide 3-kinase (PI3K) takes a key role in a plethora of physiologic processes and controls cell growth, metabolism, immunity, cardiovascular and neurological function, and more. The discovery of wortmannin as the first potent PI3K inhibitor (PI3Ki) in the 1990s provided rapid identification of PI3K-dependent processes, which drove the assembly of the PI3K/protein kinase B (PKB/Akt)/target of rapamycin (mTOR) pathway. Genetic mouse models and first PI3K isoform-specific inhibitors pinpointed putative therapeutic applications. The recognition of PI3K as target for cancer therapy drove subsequently drug development. Here we provide a brief journey through the emerging roles of PI3K to the development of clinical PI3Ki candidates.