醛固酮受体拮抗剂及醛固酮合酶抑制剂的研究进展

Research progress in aldosterone receptor antagonists and aldosterone synthase inhibitors

已有甾体类醛固酮受体拮抗剂即螺内酯和依普利酮上市,但是两者均存在一定不足。非甾体的小分子化合物作为新一代的醛固酮受体拮抗剂,finerenone、esaxerenone等都已进入临床阶段,特别是finerenone,基础研究和临床研究显示出较优的安全性和有效性,在降低高钾血症和肾功能损伤方面具有独特的优势。此外,从醛固酮生物合成途径入手,靶标醛固酮生物合成过程中的关键酶即醛固酮合酶(CYP11B2),开发选择性的CYP11B2抑制剂也是当前研究的热点。

Although aldosterone receptor antagonists,such as spironolactone and eplerenone,are available,there still exist some disadvantages.Non-steroidal small molecules have been taken as a novel generation for aldosterone receptor antagonists.Finerenone and esaxerenone are all in clinical trial stage at present,especially for finerenone,its excellent safety and effectiveness have been verified by the basic and clinical studies,which has a unique advantage in lower hyperkalemia and renal injury.In addition,it was found that aldosterone synthase(CYP11B2)is the key one for aldosterone biosynthesis from the perspective of the aldosterone biosynthesis pathway.Nowadays,the development of selective CYP11B2 inhibitors is also a research hotspot.