A potent, reversible competitive inhibitor of ABHD12 (/-hydrolase domain-containing 12) which shows negligible interaction with other serine hydrolases as determined by activity-based protein profiling.1 The IC50 of DO264 was determined to be 11 nM in isolated enzyme assays and it was shown to be active in vivo and brain penetrant. The compound was shown to produce significant elevation of brain lyso-PS/PI and C20:4 PS content in mice.2 THP-1 macrophages show increased cytokine production and mice show exacerbated immune responses to LCMV infection after treatment with DO264.1,2 Cellular studies should be limited to a concentration of 1 M which is sufficient to fully inhibit ABHD12 and avoid cytotoxicity.1 Treatment of mice may be done at 30 mg/Kg po or ip with no overt signs of toxicity.1
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