Pharmaceutical Science, Chicago College of Pharmacy Downers Grove, Midwestern University, Downers Grove, IL 60515, USA.
Pharmazz Inc. Research and Development, Willowbrook, IL 60527, USA.
Int J Mol Sci. 2022 Mar 15;23(6):3146. doi: 10.3390/ijms23063146.
Neurological/neurovascular disorders constitute the leading cause of disability and the second leading cause of death globally. Major neurological/neurovascular disorders or diseases include cerebral stroke, Alzheimer's disease, spinal cord injury, neonatal hypoxic-ischemic encephalopathy, and others. Their pathophysiology is considered highly complex and is the main obstacle in developing any drugs for these diseases. In this review, we have described the endothelin system, its involvement in neurovascular disorders, the importance of endothelin B receptors (ETBRs) as a novel potential drug target, and its agonism by IRL-1620 (INN-sovateltide), which we are developing as a drug candidate for treating the above-mentioned neurological disorders/diseases. In addition, we have highlighted the results of our preclinical and clinical studies related to these diseases. The phase I safety and tolerability study of sovateltide has shown it as a safe and tolerable compound at therapeutic dosages. Furthermore, preclinical and clinical phase II studies have demonstrated the efficacy of sovateltide in treating acute ischemic stroke. It is under development as a first-in-class drug. In addition, efficacy studies in Alzheimer's disease (AD), acute spinal cord injury, and neonatal hypoxic-ischemic encephalopathy (HIE) are ongoing. Successful completion of these studies will validate that ETBRs signaling can be an important target in developing drugs to treat neurological/neurovascular diseases.
神经系统/血管疾病是全球范围内导致残疾和死亡的主要原因。主要的神经系统/血管疾病包括中风、阿尔茨海默病、脊髓损伤、新生儿缺氧缺血性脑病等。其病理生理学被认为非常复杂,是开发这些疾病药物的主要障碍。在这篇综述中,我们描述了内皮素系统,它在神经血管疾病中的作用,内皮素 B 受体 (ETBR) 作为一个新的潜在药物靶点的重要性,以及我们正在开发的 IRL-1620(INN-sovateltide)对其的激动作用,该药物被开发为治疗上述神经疾病的候选药物。此外,我们还强调了与这些疾病相关的临床前和临床研究结果。sovateltide 的 I 期安全性和耐受性研究表明,它在治疗剂量下是一种安全且耐受良好的化合物。此外,临床前和临床 II 期研究表明,sovateltide 在治疗急性缺血性中风方面具有疗效。它正在开发作为一种首创药物。此外,在阿尔茨海默病 (AD)、急性脊髓损伤和新生儿缺氧缺血性脑病 (HIE) 中正在进行疗效研究。这些研究的成功完成将验证 ETBR 信号可以成为开发治疗神经血管疾病药物的重要靶点。
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