Phytochemical-derived nces as potential pancreatic lipase inhibitors

Overview

Sava Healthcare is exploring phytochemically derived new chemical entities (NCEs) as potential pancreatic lipase inhibitors, designed to treat obesity. Current treatments like Orlistat, the only FDA-approved drug targeting pancreatic lipase, have limitations. By screening approximately 40 phytochemicals, two have shown significant in vitro inhibition of human pancreatic lipase, though with lesser efficacy than Orlistat. The goal is to enhance these phytochemicals with modifications, incorporating β-propiolactone and Benzoxazine groups, to improve lipase inhibition.

Technical specifications

• Phytochemical Screening: Approximately 40 phytochemicals were screened through molecular docking studies.
• Key Findings: Two phytochemicals exhibited significant inhibition of human pancreatic lipase in vitro.
• Proposed Modifications: Enhancements include β-propiolactone and Benzoxazine groups to improve efficacy.
• Validation Plan: Includes stability studies, detailed molecular characterization, and toxicity profiling.
• Further Testing: Plans for in vitro and mammalian cell culture assays, with lipid profiling in obesity-induced rats.

Technology readiness level

The research is at Technology Readiness Level 3, with initial proof-of-concept demonstrated through in vitro studies. Further validation, including animal model studies and in vitro cell culture assays, is required for advancement.