Vps34-IN-4

Vps34-IN-4 is an orally active and selective VPS34 inhibitor with an IC₅₀ of 15 nM against human VPS34. Vps34-IN-4 binds to the ATP-binding pocket of VPS34. Vps34-IN-4 inhibits autophagy (autophagy) by blocking the degradation of autophagic substrates and increasing both lipidated and non-lipidated forms of LC3. Vps34-IN-4 induces time-dependent LC3-II accumulation in tumor tissues of tumor-bearing mice. Vps34-IN-4 can be used for research on cancers such as colon cancer^[1]. In Vitro:Vps34-IN-4 (Compound 19) (1-10 μM; 24 h) potently inhibits autophagy in DLD1 cells and induces concentration-dependent accumulation of autophagic substrates and LC3^[1].
Vps34-IN-4 potently inhibits VPS34 activity in U2OS cells with an IC₅₀ of 25 nM in the GFP-FYVE reporter assay^[1]. In Vivo:Vps34-IN-4 (50 mg/kg; p.o.; twice daily; for 7 consecutive days) inhibits autophagy in RKO colon tumor xenografts in vivo^[1].