Novel Anti-Ovarian Epithelial Adenocarcinoma Agent: HM-10/10 HDL-Mimetic Peptide—Pharmacokinetic and Pharmacodynamic Characterization [ID: 1377510]

Abstract

INTRODUCTION: Epithelial adenocarcinoma of the ovary (EOC) is the second most common cancer affecting the female reproductive system and is associated with the fifth highest rate of cancer-related deaths in women. With many women presenting in late stages, the estimated chance of survival for 2, 5, and 10 years were 65%, 44%, and 36%, respectively. In recent literature, the role of HDL-associated apolipoproteins has been shown to be effective in the treatment of proinflammatory diseases, including cancer. Previously we developed a novel 20-amino acid mimetic peptide, HM-10/10, which was able to inhibit tumor development and growth in EOC models in vitro and in vivo. These findings prompted our decision to further our research by performing characterization to advance HM-10/10 as our apolipoprotein mimetic peptide candidate of choice for use as a novel therapeutic agent against EOC. The aim of this study was to report the pharmacokinetic (PK) and pharmacodynamic (PD) properties of HM-10/10 relative to its stability in vitro. METHODS: To evaluate PK/PD, multiple procedures were performed in vitro. RESULTS: The results demonstrated PK/PD good stability in plasma and the gastric environment. However, under conditions modeling the small intestine, HM-10/10 demonstrated significant degradation, likely because of the diverse array of peptidases encountered therein. CONCLUSION: These data highlight the PK/PD of HM-10/10 and demonstrate its potential as an effective therapeutic for treating EOC. The preferred route of delivery of HM-10/10 is oral, and toward that end, HM-10/10 demonstrated remarkable stability over a broad physiologic pH range; however, its stability was significantly degraded by conditions simulating the small intestine.