Mechanism of action: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PI3Kɣ) inhibitor

Preclinical pharmacology and pharmacokinetics

AZD3458 is an inhibitor of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma which inhibits isolated gamma enzyme with an IC50 of 7.9nM, and phosphorylation of Akt in cells with an IC50 of 8nM.  It is selective against catalytic subunits alpha, beta and delta (enzyme IC50 of 7.9mM, <30mM and 0.3mM respectively; cell IC50 <30mM, <30mM and 1mM respectively).  Human neutrophil activation is inhibited with an IC50 of 50nM.

Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response.  The protein encoded by this gene is a class I catalytic subunit of PI3K.  Like other class I catalytic subunits (p110-alpha p110-beta, and p110-delta), the encoded protein binds a p85 regulatory subunit to form PI3K.

Suitable for and exclusions

Restricted to preclinical studies (proposals) only.

Additional Information

Gene information from the NCBi

This compound works on the following genes: