LaCagnin L B, Levitt M, Bergstrom J M, Colby H D
Department of Pharmacology and Toxicology, Philadelphia College of Pharmacy and Science, PA 19104.
J Steroid Biochem. 1989 Oct;33(4A):599-604. doi: 10.1016/0022-4731(89)90047-2.
SU-10'603 is a pyridine derivative that is widely used as a steroid 17 alpha-hydroxylase inhibitor. Studies were done to evaluate its effects in vitro on several other monooxygenases in guinea pig adrenal mitochondrial and microsomal preparations. In adrenal mitochondria, SU-10'603 produced a concentration-dependent inhibition of 11 beta-hydroxylation; 50% inhibition was obtained at a concentration of approximately 0.5 mM. Its potency was similar to that of the 11 beta-hydroxylase inhibitor, metyrapone. SU-10'603 was a more potent inhibitor of cholesterol sidechain cleavage (CSC) than of 11 beta-hydroxylation; a 50% decline in CSC activity was produced by an inhibitor concentration of approximately 0.1 mM. In adrenal microsomal preparations, SU-10'603 had no effect on the rate of 21-hydroxylation of 17 alpha-hydroxyprogesterone. However, SU-10'603 was a potent inhibitor of adrenal microsomal xenobiotic metabolizing monooxygenases (benzo[a]pyrene hydroxylase, benzphetamine demethylase), effecting approximately 50% inhibition of both reactions at a concentration of 0.05 mM. The results indicate that SU-10'603 inhibits several monooxygenases in the guinea pig adrenal cortex and is thus not specific for 17 alpha-hydroxylation.
SU - 10'603是一种吡啶衍生物，被广泛用作类固醇17α - 羟化酶抑制剂。已开展研究以评估其在体外对豚鼠肾上腺线粒体和微粒体制剂中其他几种单加氧酶的作用。在肾上腺线粒体中，SU - 10'603对11β - 羟化作用产生浓度依赖性抑制；在浓度约为0.5 mM时可获得50%的抑制率。其效力与11β - 羟化酶抑制剂美替拉酮相似。SU - 10'603对胆固醇侧链裂解（CSC）的抑制作用比对11β - 羟化作用更强；抑制剂浓度约为0.1 mM时可使CSC活性下降50%。在肾上腺微粒体制剂中，SU - 10'603对17α - 羟孕酮的21 - 羟化速率没有影响。然而，SU - 10'603是肾上腺微粒体异生物质代谢单加氧酶（苯并[a]芘羟化酶、苄非他明脱甲基酶）的有效抑制剂，在浓度为0.05 mM时对这两种反应的抑制率约为50%。结果表明，SU - 10'603抑制豚鼠肾上腺皮质中的几种单加氧酶，因此并非特异性作用于17α - 羟化。
