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Article

Discovery of Pyridopyrimidinones that Selectively Inhibit the H1047R PI3Kα Mutant Protein.

Journal of medicinal chemistry - 28 Mar 2024

Ketcham John M, Harwood Stephen J, Aranda Ruth, Aloiau Athenea N, Bobek Briana M, Briere David M, Burns Aaron C, Caddell Haatveit Kersti, Calinisan Andrew, Clarine Jeffery, Elliott Adam, Engstrom Lars D, Gunn Robin J, Ivetac Anthony, Jones Benjamin, Kuehler Jon, Lawson J David, Nguyen Natalie, Parker Cody, Pearson Kelly E, Rahbaek Lisa, Saechao Barbara, Wang Xiaolun, Waters Anna, Waters Laura, Watkins Ashlee H, Olson Peter, Smith Christopher R, Christensen James G, Marx Matthew A

Abstract excerpt

The H1047R mutation of PIK3CA is highly prevalent in breast cancers and other solid tumors. Selectively targeting PI3KαH1047R over PI3KαWT is crucial due to the role that PI3KαWT plays in normal cellular processes, including glucose homeostasis. Currently, only one PI3KαH1047R-selective inhibitor has progressed into clinical trials, while three pan mutant (H1047R, H1047L, H1047Y, E542K, and E545K) selective PI3Kα...

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Identifiers

PMID: 38477582
DOI: 10.1021/acs.jmedchem.4c00078
PMCID: PMC10983000

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-07.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

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