Tregeagle Dane, Doherty Catherine, Callis Timothy, Kassiou Michael
School of Chemistry, The University of Sydney, Sydney, NSW, Australia.
School of Chemistry, The University of Sydney, Sydney, NSW, Australia.
J Pharmacol Sci. 2025 Jul;158(3):238-258. doi: 10.1016/j.jphs.2025.04.004. Epub 2025 Apr 14.
The ability to target the oxytocin and vasopressin receptors is of high therapeutic value due to their clinical relevance in wide range of neuropsychiatric conditions spanning from anxiety to schizophrenia. Despite the massive therapeutic potential in modulating this system, the only clinically approved small molecule-based therapeutics (Mozavaptan, Conivaptan and Tolvaptan) are for use in the periphery. Cyclotide mimetics of the native neuropeptides are well explored in the literature although these scaffolds are unsuitable for application to the central nervous system. This work highlights non-peptidic natural products that are active within the neurohypophysial system that may be used to inspire future drug discovery endeavours.
由于催产素和血管加压素受体在从焦虑到精神分裂症等广泛的神经精神疾病中具有临床相关性，因此靶向这些受体的能力具有很高的治疗价值。尽管调节该系统具有巨大的治疗潜力，但目前唯一获得临床批准的基于小分子的疗法（莫扎伐普坦、考尼伐坦和托伐普坦）仅用于外周。天然神经肽的环肽模拟物在文献中已有充分研究，尽管这些支架不适用于中枢神经系统。这项工作突出了在神经垂体系统中具有活性的非肽类天然产物，这些产物可能用于启发未来的药物发现工作。
