Serabelisib

Serabelisib (MLN1117) is a selective p110α inhibitor with an IC₅₀ of 15 nM. IC50 & Target: IC50: 15 nM (p110α), 4500 nM (p110β), 1900 nM (p110γ), 13900 nM (p110δ), 1670 nM (mTOR)^[1] In Vitro: Serabelisib (MLN1117) inhibits Akt phosphorylation and growth in PIK3CA mutant breast cancer cells with IC₅₀s around 2 μM, yet has no effect on cells lacking PTEN. BCR-stimulated B cells treated with 1 μM Serabelisib (MLN1117) displays a significant reduction (up to 50%) in the magnitude of the phosphorylated Akt (p-Akt) signal measured by intracellular flow cytometry. The effect of Serabelisib is dose-dependent^[1]. In Vivo: Treatment with Serabelisib (MLN1117) at 30 and 60 mg/kg causes little reduction of TNP-specific IgG3. Notably, reduction of TNP-specific IgG3 at higher doses of Serabelisib (MLN1117) (120 mg/kg) is observed, consistent with the partial reduction in cell division in B cells treated with Serabelisib before anti-IgM stimulation. However, 120 mg/kg is above the effective dose of Serabelisib (MLN1117) for tumor growth inhibition (30-60 mg/kg)^[1].