The serine hydrolase known as α/β-hydrolase domain-containing protein 6 (ABHD6) hydrolyzes 2-arachidonoyl glycerol to regulate its availability at cannabinoid receptors. WWL123 is a brain-penetrant inhibitor of ABHD6 (IC50 = 0.43 μM) that demonstrates >10-fold selectivity for ABHD6 compared to a panel of ~35 other serine hydrolases. Inhibition of ABHD6 by WWL123 has been used to decrease seizure incidence in a genetic mouse model of juvenile Huntington’s disease as well as in chemically-induced epilepsy models.
