2. Academic Validation
  3. Design and synthesis of endocannabinoid enzyme inhibitors for ocular indications

Design and synthesis of endocannabinoid enzyme inhibitors for ocular indications

  • Bioorg Med Chem Lett. 2022 Jul 15;68:128763. doi: 10.1016/j.bmcl.2022.128763.
Alan Fulp 1,  Sarah Bingham 2,  Bethany Fisler 2,  Felice Kho 2,  Joshua Kim 2,  So Jung Kim 2,  Tabitha Martin 2,  Bailey Mims 2,  Kezia Reji Thomas 2,  Grace Roe 2,  Julia Spiotta 2,  Julianna Young 2,  Matthew Lazenka 3
Affiliations

Affiliations

  • 1 Department of Biology and Chemistry, Liberty University, 1971 University Blvd, Lynchburg, VA 24515, USA. Electronic address: [email protected].
  • 2 Department of Biology and Chemistry, Liberty University, 1971 University Blvd, Lynchburg, VA 24515, USA.
  • 3 Kentucky College of Osteopathic Medicine and Kentucky College of Optometry, University of Pikeville, 147 Sycamore Street, Pikeville, KY 41501, USA.
PMID: 35500728 DOI: 10.1016/j.bmcl.2022.128763
Abstract

A small library of FAAH and dual FAAH/MAGL inhibitors designed for peripheral selectivity were targeted. Of these compounds, three were identified to have desirable FAAH inhibition and reduced permeability in a PAMPA assay. Those three compounds were advanced into a MAGL Inhibitor assay and one was found to be a relative selective FAAH Inhibitor, FAAH to MAGL IC50 ratio of 1:27, and one was found to be more characteristic of a true dual Enzyme inhibitor, FAAH to MAGL IC50 ratio of 1:4. Both compounds showed activity in an ABPP assay, blockage of TAMRA-FP labeling of FAAH and MAGL in rat eye homogenate.

Keywords

Endocannabinoid system; FAAH; Inhibitor; MAGL; Peripheral; Topological polar surface area.

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