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CH5132799 is a selective class I PI3K inhibitor. CH5132799 inhibits class I PI3Ks, particularly PI3Kα, with an IC₅₀ of 14 nM.

CH5132799 is a selective class I PI3K inhibitor with potent antitumor activity against tumors harboring the PIK3CA mutations. CH5132799 selectively inhibits class I PI3Ks and PI3Kα mutants in in vitro kinase assays. CH5132799 inhibits class I PI3Ks, particularly PI3Kα, with an IC₅₀ of 14 nM. IC₅₀ values against class II PI3Ks (C2α and C2β), a class III PI3K (Vps34), and a class IV PI3K (mTOR) are more than 100-fold higher than that against PI3Kα. Interestingly, slightly lower IC₅₀ values are observed against PI3Kα with oncogenic mutations E542K, E545K, and H1047R than against wild-type (WT) PI3Kα. 

In an analysis of cocrystal structure with PI3Kγ (PBD ID: 3APC), CH5132799 is shown to interact with ATP-binding sites of the enzyme, suggesting an ATP competitive mode of inhibition. No significant inhibitory activities of CH5132799 are observed against a representative panel of 26 protein kinases, including RTKs, nonreceptor tyrosine kinases, and serine/threonine kinases. These data indicate that CH5132799 is a selective class I PI3K inhibitor, especially against PI3Kα and its mutants. CH5132799 shows superior antiproliferative activity across the 4 tumor types, with 75% (45/60) of lines having an IC₅₀ below 1 μM and 38% (23/60) of lines having an IC₅₀ below 0.3 μM^[1].