IHMT-PI3K-455 (Compound 15u) is a potent, selective PI3Kγ/δ dual inhibitor with IC50 values of 7.1 nM for PI3Kγ and 0.57 nM for PI3Kδ, exhibiting oral activity. This compound inhibits AKT phosphorylation and promotes tumor regression by recruiting and activating CD8+ T cells. It is utilized in cancer research [1].

PI3Kβ:42.04 nM, PI3Kα:6.717 μM, PI3Kγ:7.1 nM, PI3Kδ:0.57 nM

IHMT-PI3K-455 at a concentration of 1 μM for 2 hours inhibited AKT phosphorylation mediated by PI3Kγ/δ in RAW264.7 and Raji cells [1]. Additionally, when applied at the same concentration for 72 hours, it altered the polarization of M2 macrophages derived from THP-1 and BMDM cells [1].

IHMT-PI3K-455 administered orally at a dose of 40 mg/kg once daily for 30 consecutive days inhibited tumor growth in the MC38 colorectal cancer murine allograft model [1]. This compound suppressed tumor proliferation by recruiting and activating an increased number of CD8+ cytotoxic T cells [1]. Additionally, pharmacokinetic parameters were assessed in Sprague-Dawley rats, revealing for a 1 mg/kg intravenous dose: Cmax (1233 ng/mL), Tmax (0.03 h), AUC0-∞ (477 h⋅ng/mL), T1/2 (1.59 h), CL (2.12 L/h/kg), Vz (4.80 L/kg); and for a 10 mg/kg oral dose: Cmax (157 ng/mL), Tmax (3.42 h), AUC0-∞ (838 h⋅ng/mL), T1/2 (2.71 h), CL (14.76 L/h/kg), Vz (56.02 L/kg), and F (17.6%).