PHY34 is a late stage autophagy inhibitor with nanomolar level inhibitory effect and anti-tumor activity against high-grade serous ovarian cancer (HGSOC) in vivo.

In HGSOC cell lines, PHY34 showed cytotoxicity with IC50 of 4 nM. Its IC50 values in MDA-MB-435 and MDAMB-231 cell lines were 23 nM and 5.2 nM, respectively. In OVCAR3 cells, 100 nM PHY34 increased the level of early and late apoptotic cells [1].

In the hollow fiber deflector, PHY34 significantly inhibited the growth of cancer cells; In the transplanted tumor model, PHY34 reduced the ovarian tumor load. The bioavailability of mice was 56.6% after intravenous injection of 0.6 mg/kg, intraperitoneal injection of 1.8 mg/kg or oral administration of 75 mg/kg PHY34, and 2.5% after oral administration. After oral administration, the systemic clearance (CL) was 194.1 L/hr/kg, which was nearly 40 times the liver blood flow of mice, indicating that PHY34 had significant extrahepatic clearance. After oral administration, PHY34 was rapidly absorbed, and Tmax was 0.25 hr [1].