Sharp R B, Senior M B, Penning T M
Biochem J. 1985 Sep 15;230(3):587-94. doi: 10.1042/bj2300587.
2 alpha-Cyanoprogesterone potently inhibits the conversion of [3H]pregnenolone into progesterone catalysed by bovine corpora lutea, bovine adrenal cortex and human term placenta microsomes (microsomal fractions), yielding IC50 (concentration causing 50% inhibition) values of 66 nM, 120 nM and 700 nM respectively. By contrast, it is an exceedingly poor inhibitor of the isomerization of pregn-5-ene-3,20-dione, yielding IC50 values between 50 and 70 microM. On this basis, 2 alpha-cyanoprogesterone would appear to be an extraordinarily selective inhibitor of the 3 beta-hydroxysteroid dehydrogenase. Dixon plots indicate that it is a very-tight-binding competitive inhibitor of the corpus-luteum enzyme, yielding a Ki of 15 nM. In the bovine adrenal cortex and human placenta the steroid is less potent and inhibits the dehydrogenase non-competitively with Ki values of 150 nM and 1.0 microM respectively. Thus 2 alpha-cyanoprogesterone inhibits the corpus-luteum dehydrogenase with substantial selectivity. Because of its high affinity for the ovarian enzyme, the presence of low-micromolar concentrations of 2 alpha-cyanoprogesterone can promote a complete cessation of progesterone synthesis in corpora-lutea microsomes for several hours. Since this effect is observed in the presence of saturating concentrations of pregnenolone (50 microM), it is predicted that this inhibitor may be even more potent in vivo. 2 alpha-Cyanoprogesterone displays very low affinity for the human progesterone receptor, yielding a Kd of 600 nM as against a Kd of 1.6 nM for progesterone. It is suggested that 2 alpha-cyanoprogesterone may be a selective inhibitor of ovarian progesterone synthesis and may act as an effective anti-gestational agent in vivo.
2α-氰基孕酮能有效抑制牛黄体、牛肾上腺皮质和人足月胎盘微粒体（微粒体部分）催化的[3H]孕烯醇酮向孕酮的转化，其IC50（引起50%抑制的浓度）值分别为66 nM、120 nM和700 nM。相比之下，它对孕-5-烯-3,20-二酮异构化的抑制作用极弱，IC50值在50至70 μM之间。基于此，2α-氰基孕酮似乎是一种极具选择性的3β-羟基类固醇脱氢酶抑制剂。迪克森图表明它是黄体酶的一种紧密结合的竞争性抑制剂，Ki为15 nM。在牛肾上腺皮质和人胎盘中，该类固醇的效力较低，分别以150 nM和1.0 μM的Ki值非竞争性抑制脱氢酶。因此，2α-氰基孕酮对黄体脱氢酶具有显著的选择性抑制作用。由于其对卵巢酶具有高亲和力，低微摩尔浓度的2α-氰基孕酮的存在可促使黄体微粒体中孕酮合成完全停止数小时。由于在孕烯醇酮饱和浓度（50 μM）存在的情况下观察到这种效应，预计该抑制剂在体内可能更有效。2α-氰基孕酮对人孕酮受体的亲和力非常低，Kd为600 nM，而孕酮的Kd为1.6 nM。有人提出，2α-氰基孕酮可能是卵巢孕酮合成的选择性抑制剂，在体内可能作为一种有效的抗孕剂。
