Sovateltide Mediated Endothelin B Receptors Agonism and Curbing Neurological Disorders

Amaresh K Ranjan, Anil Gulati, Amaresh K Ranjan, Anil Gulati

Abstract

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.

Keywords: IRL-1620; endothelin B receptors; neurogenesis; neurological diseases; neurovascular disorders; regeneration; sovateltide; stem/progenitor cells.

Conflict of interest statement

A.G. is a Pharmazz, Inc. employee and has issued and pending patents related to the studies described in this review. A.K.R. declares no competing interests.

Figures

Figure 1
Figure 1
Chemical structure of sovateltide.( Adapted with permission from MedKoo Biosciences, Inc. © MedKoo Biosciences, Inc. https://www.medkoo.com/products/34963, accessed on 10 March 2022).
Figure 2
Figure 2
Diagrammatic representation of the effect of sovateltide on neuronal progenitor cell differentiation and neural regeneration after cerebral ischemic stroke. (A) Normal homeostasis, (B) Higher damage than regeneration (probably due to less differentiation of NPCs), (C) Higher regeneration and lower damage after sovateltide treatment (probably due to higher NPCs differentiation), which remains similar after saline treatment (D).

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