Enhancing Drug Discovery and Development through the Integration of Medicinal Chemistry, Chemical Biology, and Academia-Industry Partnerships: Insights from Roche's Endocannabinoid System Projects

Chimia (Aarau). 2024 Aug 21;78(7-8):499-512. doi: 10.2533/chimia.2024.499.

Abstract

The endocannabinoid system (ECS) is a critical regulatory network composed of endogenous cannabinoids (eCBs), their synthesizing and degrading enzymes, and associated receptors. It is integral to maintaining homeostasis and orchestrating key functions within the central nervous and immune systems. Given its therapeutic significance, we have launched a series of drug discovery endeavors aimed at ECS targets, including peroxisome proliferator-activated receptors (PPARs), cannabinoid receptors types 1 (CB1R) and 2 (CB2R), and monoacylglycerol lipase (MAGL), addressing a wide array of medical needs. The pursuit of new therapeutic agents has been enhanced by the creation of specialized labeled chemical probes, which aid in target localization, mechanistic studies, assay development, and the establishment of biomarkers for target engagement. By fusing medicinal chemistry with chemical biology in a comprehensive, translational end-to-end drug discovery strategy, we have expedited the development of novel therapeutics. Additionally, this strategy promises to foster highly productive partnerships between industry and academia, as will be illustrated through various examples.

Keywords: Academia-industry collaboration; CB1R; CB2R; Endocannabinoid system; Labeled chemical probe; MAGL; PPAR.

MeSH terms

  • Academia
  • Chemistry, Pharmaceutical*
  • Drug Development
  • Drug Discovery*
  • Drug Industry
  • Endocannabinoids* / chemistry
  • Endocannabinoids* / metabolism
  • Humans
  • Monoacylglycerol Lipases / antagonists & inhibitors
  • Monoacylglycerol Lipases / metabolism

Substances

  • Endocannabinoids
  • Monoacylglycerol Lipases