Dinan Laurence, Dioh Waly, Veillet Stanislas, Lafont Rene
Biophytis, Sorbonne Université, BC9, 4 place Jussieu, 75005 Paris, France.
BIOSIPE, IBPS, Sorbonne Université, UPMC, 75005 Paris, France.
Biomedicines. 2021 Apr 29;9(5):492. doi: 10.3390/biomedicines9050492.
There is growing interest in the pharmaceutical and medical applications of 20-hydroxyecdysone (20E), a polyhydroxylated steroid which naturally occurs in low but very significant amounts in invertebrates, where it has hormonal roles, and in certain plant species, where it is believed to contribute to the deterrence of invertebrate predators. Studies in vivo and in vitro have revealed beneficial effects in mammals: anabolic, hypolipidemic, anti-diabetic, anti-inflammatory, hepatoprotective, etc. The possible mode of action in mammals has been determined recently, with the main mechanism involving the activation of the Mas1 receptor, a key component of the renin-angiotensin system, which would explain many of the pleiotropic effects observed in the different animal models. Processes have been developed to produce large amounts of pharmaceutical grade 20E, and regulatory preclinical studies have assessed its lack of toxicity. The effects of 20E have been evaluated in early stage clinical trials in healthy volunteers and in patients for the treatment of neuromuscular, cardio-metabolic or respiratory diseases. The prospects and limitations of developing 20E as a drug are discussed, including the requirement for a better evaluation of its safety and pharmacological profile and for developing a production process compliant with pharmaceutical standards.
20-羟基蜕皮激素（20E）是一种多羟基类固醇，在无脊椎动物中天然存在，含量虽低但具有重要意义，在其中发挥激素作用；在某些植物物种中也有发现，据信它有助于抵御无脊椎动物捕食者。目前，人们对其在制药和医学领域的应用兴趣与日俱增。体内和体外研究均显示，20E对哺乳动物具有有益作用，如合成代谢、降血脂、抗糖尿病、抗炎、保肝等。最近已确定其在哺乳动物中的可能作用模式，主要机制涉及激活Mas1受体，该受体是肾素-血管紧张素系统的关键组成部分，这可以解释在不同动物模型中观察到的许多多效性效应。现已开发出大量生产药用级20E的工艺，临床前监管研究也评估了其无毒性。在健康志愿者和患者的早期临床试验中，已对20E用于治疗神经肌肉、心脏代谢或呼吸系统疾病的效果进行了评估。本文讨论了将20E开发成药物的前景和局限性，包括需要更好地评估其安全性和药理学特征，以及开发符合制药标准的生产工艺。
