DO-264

DO-264 是一个具有体内活性的、自水解酶结构域 12 (ABHD12) 的抑制剂，其 IC50 值为 11 nM。 DO-264 is a selective and in vivo-active inhibitor of Abhydrolase Domain Containing 12 ( ABHD12 ), with an IC 50 of 11 nM. In Vitro DO-264 displays an IC 50 value of 11 nM (9.6 nM-13 nM). DO-264 blocks lyso-PS hydrolysis activities of recombinant mouse and human ABHD12 in transfected HEK293T cell lysates (DO-264 IC 50 values of ~30 and 90 nM against mouse and human ABHD12, respectively) and the ABHD12-dependent lyso-PS lipase activity of membrane lysates from mouse brain (IC 50 =2.8 nM, 2.4 nM-3.3 nM) and human THP-1 cells (IC 50 = 8.6 nM, 6.3 nM-12 nM). MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo Mice treated with DO-264 display dose-dependent increases in brain lyso-PS and 20:4 PS content that are qualitatively similar to the changes observed in ABHD12 –/– mice. DO-264-treated mice, however, show minimal impairment in auditory function following four weeks of drug exposure. Both ABHD12 –/– and DO-264-treated mice display exacerbated immunopathology following infection with the lymphocytic choriomeningitis virus (LCMV) clone 13, resulting in severe inflammatory lung damage, heightened chemokine production, and, in some cases, death . MCE has not independently confirmed the accuracy of these methods. They are for reference only. IC50& Target:IC50: 11 nM (ABHD12)

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