WWL70

WWL70 is a selective alpha/beta hydrolase domain 6 (ABHD6) inhibitor with an IC₅₀ of 70 nM. IC50 & Target: IC50: 70 nM (ABHD6)^[1] In Vitro: At 1 h after WWL70 (10 μM) treatment, 2-Arachidonoylglycerol (2-AG) is increased by 20% compare to untreated cells. At either 1 or 10 μM, WWL70 completely blocks the lipopolysaccharide (LPS)-induced increase of PGE₂. The enhanced mRNA expression of mPGES-1 and mPGES-2 by LPS is also reduced by WWL70. The IC₅₀ of WWL70 to inhibit the PGE₂ biosynthesis is about 100 nM^[2]. In Vivo: Although post-treatment with WWL70 at 5 mg/kg does not have any effect, treatment with WWL70 at 10 mg/kg improves the performance significantly. WWL70 treatment improves motor coordination of traumatic brain injury (TBI) mice in a concentration dependent manner. The latency to fall in animals treated with WWL70 at 5 mg/kg increases from 74.92±4.8 to 99.57±5.21 on day 3 (p<0.01) and from 87.32±4.42 to 100.14±3.56 on day 7 (p<0.05) post-injury when compare with the vehicle-TBI groups. At 10 mg/kg, WWL70 treatment improves motor coordination starting on day 1 post-injury. WWL70 treatment completely restores the ability of TBI mice to continuously alternate arms during Y maze exploration (69.67±4.98 %)^[3].