SMP-028是中性胆固醇脂酶的抑制剂(CEase)，其IC50值为1.01μM。
SMP-028 is an inhibitor of neutral cholesterol esterase (CEase), with an IC50 of 1.01 μM.
SMP-028 potently and concentration-dependently inhibits neutral cholesterol esterase (CEase) with an IC50 value of 1.01 μM. On the other hand, inhibition of other steroidogenic enzymes by SMP-028 is weak with IC50 values>10 μM. In particular, SMP-028 does not inhibit acid CEase and only weakly reduces the activity of CYP11A1 (IC50 values>100 μM and 49.8 μM respectively) [1]. SMP-028 at 10 μM or less does not affect the viability of male adrenal cells, female adrenal cells, testicular cells, and ovarian cells. On the other hand, SMP-028 at concentrations higher than 30 μM significantly reduce the viability of male adrenal cells, female adrenal cells [2].
[1]. Nishizato Y, et al. Translational research into species differences of endocrine toxicity via steroidogenesis inhibition by SMP-028--for human safety in clinical study. Toxicol Appl Pharmacol. 2014 May 1;276(3):213-9. [2]. Nishizato Y, et al. Effect of SMP-028 on steroidogenesis in rats; mechanism of toxicological events on endocrine organs of rats. Toxicol In Vitro. 2014 Apr;28(3):397-402.
Cell experiment: | Testicular and ovarian cells from Sprague–Dawley rats are cultured in medium containing SMP-028 dissolved in dimethyl sulfoxide (DMSO) is added to each well of the 96-well cell culture plates. The final concentration of DMSO is 0.1% (v/v) and that of SMP-028 is set between 0.1 μM to 50 μM. The cells with culture medium containing DMSO only (not containing SMP-028) are as a control. The plates are next incubated at 37°C, 5% CO2 in air atmosphere for 24 hours. SMP-028 cytotoxicity is estimated. The luminescence of each plate is measured[2]. |
参考文献: [1]. Nishizato Y, et al. Translational research into species differences of endocrine toxicity via steroidogenesis inhibition by SMP-028--for human safety in clinical study. Toxicol Appl Pharmacol. 2014 May 1;276(3):213-9. | |
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