Stearoyl-CoA desaturase (SCD) is a lipogenic enzyme involved in the de novo lipogenesis of monounsaturated fatty acids (MUFAs) and catalyzes insertion of the cis double bond at the delta-9 position (between carbons 9 and 10) of saturated fatty acids (SFAs)[1]. SCD1 inhibitor-4 is a potent, orally active SCD1 inhibitor. SCD1 inhibitor-4 can be used for the research of diabetes. SCD1 inhibitor-4 (1~30 mg/kg) shows a dose-dependent decrease in desaturation index with a 55 % reduction at 1 mg/kg and 85% reduction at the 10 and 30 mg/kg doses[2]. SCD1 inhibitors have potential effects on obesity, diabetes, acne, and cancer, but the adverse effects associated with SCD1 inhibition in the skin and eyelids are impediments to clinical development. SCD1 inhibitor-4 was administered orally to rats fed a high sucrose very low fat (HSVLF) diet for 8 days. Rats fed a HSVLF diet had hepatic TG content of approximately 80 mg/g tissue and it significantly attenuated hepatic TG accumulation in a dose-dependent manner. SCD1 inhibitor-4 did not have significant adverse events during the treatment period at 100 mg/kg, and only very slight loss of fur in one out of five rats from day 9 and thereafter at a dose of 1000 mg/kg. Comparing plasma exposure at the no-observed adverse effect level (NOAEL) of 100 mg/kg (179 mM h) with the plasma exposure at therapeutic doses, SCD1 inhibitor-4 had a favorable safety margin (10e81-fold, AUC levels)[3].
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