AZD3458
Preclinical pharmacology and pharmacokinetics
AZD3458 is an inhibitor of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PI3Kɣ) 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
AZD3458 is available for preclinical studies only.
Mechanism of Action
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PI3Kɣ) inhibitor
Original Therapeutic Area
Other
CNS Penetrant
Low
Route of administration
Oral
Modality
Small Molecule
Additional Information
1. Carnevalli LS., et al. (2021).
Macrophage Activation Status Rather than Repolarization Is Associated with Enhanced Checkpoint Activity in Combination with PI3Kγ Inhibition. Mol Cancer Ther. 2021, 30. doi: 10.1158/1535-7163.MCT-20-0961. Epub ahead of print. PMID: 33785652.