School of Pharmaceutical Sciences, Universiti Sains Malaysia, USM, Penang, 11800, Malaysia.
Future Med Chem. 2023 May;15(9):791-808. doi: 10.4155/fmc-2023-0016. Epub 2023 May 25.
It is well established that endogenously produced dynorphin 1-17 (DYN 1-17) is susceptible to enzymatic degradation, producing a variety of unique fragments in different tissue matrices and disease pathologies. DYN 1-17 and its major biotransformation fragments have significant roles in neurological and inflammatory disorders upon interacting with opioid and non-opioid receptors at both central and peripheral levels, thus highlighting their potential as drug candidates. Nevertheless, their development as promising therapeutics is challenged by several issues. This review aims to provide the latest and comprehensive updates on DYN 1-17 biotransformed peptides, including their pharmacological roles, pharmacokinetic studies and relevant clinical trials. Challenges in their development as potential therapeutics and proposed solutions to overcome these limitations are also discussed.
内源性产生的强啡肽 1-17（DYN 1-17）很容易被酶降解，在不同的组织基质和疾病病理中产生各种独特的片段。DYN 1-17 及其主要生物转化片段在与中枢和外周水平的阿片和非阿片受体相互作用时，在神经和炎症性疾病中具有重要作用，因此凸显了它们作为药物候选物的潜力。然而，由于存在一些问题，它们作为有前途的治疗药物的开发仍面临挑战。本综述旨在提供 DYN 1-17 生物转化肽的最新和全面的更新信息，包括它们的药理学作用、药代动力学研究和相关临床试验。还讨论了它们作为潜在治疗药物开发的挑战以及克服这些限制的建议解决方案。
