Profiling the anandamide reuptake inhibitor WOBE437

ABSTRACT: Anandamide, or N-arachidonoylethanolamine (AEA), is a signaling lipid that modulates neurotransmitter release via activation of the cannabinoid receptor type 1 (CB1R) in the brain. Termination of anandamide signaling is thought to be mediated via a facilitated cellular reuptake process utilizing an unknown transporter protein. Recently, WOBE437 has been reported as a novel, natural product-based inhibitor of AEA reuptake that is active in cellular and in vivo models. To profile its target interaction landscape, we synthesized pac-WOBE, a photoactivatable probe derivative of WOBE437, and performed chemical proteomics in mouse neuroblastoma Neuro-2a cells. Surprisingly, WOBE437, but not OMDM-1, was found to increase AEA uptake in Neuro-2a cells. In line, WOBE437 reduced cellular levels of AEA and related N-acylethanolamines (NAEs). Using pac-WOBE, we identified saccharopine dehydrogenase-like oxidoreductase (SCCPDH), vesicle amine transport 1 (VAT1) and ferrochelatase (FECH) as WOBE437-interacting proteins in Neuro-2a cells

INSTRUMENT(S): Synapt MS

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Neuron Development, Cell Culture

DISEASE(S): Neuroblastoma

SUBMITTER: Berend Gagestein  

LAB HEAD: Mario van der Stelt

PROVIDER: PXD031488 | Pride | 2022-05-04

REPOSITORIES: Pride