About INT-767
About INT-767
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The amounts of ALT and AST inside the plasma of apoE KO mice didn't clearly show statistic changes compared Together with the Manage team.
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Summary The sphingomyelin synthase 2 (SMS2) is a possible focus on for pharmacological intervention in atherosclerosis. On the other hand, thus far, number of selective SMS2 inhibitors and their pharmacological actions were claimed. During this review, a class of two-benzyloxybenzamides have been found as novel SMS2 inhibitors via scaffold hopping and structural optimization. Among them, Ly93 as one of the most powerful inhibitors exhibited IC50 values of 91 nM and 133.9 μM against purified SMS2 and SMS1 respectively. The selectivity ratio of Ly93 was more than 1400-fold for purified SMS2 around SMS1. The in vitro reports indicated that Ly93 not just dose-dependently diminished apoB secretion from Huh7 cells, but will also appreciably diminished the SMS exercise and enhanced cholesterol efflux from macrophages. In the meantime, Ly93 inhibited the secretion of LPS-mediated pro-inflammatory cytokine and chemokine in macrophages. The pharmacokinetic profiles of Ly93 done on C57BL/6J mice shown that Ly93 was orally efficacious. Being a strong selective SMS2 inhibitor, Ly93 drastically decreased the plasma SM levels of C57BL/6J mice.
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On top of that, Ly93 drastically reduced the plasma SM amounts of C57BL/6J mice. Furthermore, Ly93 was effective at dose-dependently attenuating the atherosclerotic lesions in the root and the entire aorta together with macrophage material in lesions, in apolipoprotein E gene knockout mice treated with Ly93.
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