AZD3458 is an orally bioavailable potent and selective PI3Kγ inhibitor, and an immuno-oncology modulator. It selectively inhibits PI3Kγ with a cellular IC50 of 8 nM, a 100-fold selective over PI3Kδ in vitro, AZD3458 inhibits pAKTS308/S473 in human macrophages and mouse CD11b activation at 32nM and 30nM free IC50 respectively. Application of AZD3458 in vivo with checkpoint inhibitors α-PD-1 or α-PD-L1 had greater anti-tumor effects than checkpoint inhibitor alone in 4T1, LLC, CT-26 and MC-38 mouse syngeneic models, suggesting that AZD3458 can reverse myeloid suppressive tumor microenvironment and revert tumor resistance to immunotherapy in myeloid-enriched immunosuppressive tumor types.

KEYWORDS: AZD3458 | Supplier | PI3Kγ inhibitor | AZD-3458 | AZD 3458 | CT-A3458 | CAS [2132961-46-5] | Phosphatidylinositol | PI3K | Inhibitor | Enzymes