Department of Pharmaceutical Chemistry, Akshaya Institute of Pharmacy, Tumkur, Karnataka, India.
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Oct;397(10):7337-7351. doi: 10.1007/s00210-024-03129-0. Epub 2024 May 13.
As peptide-based therapies gain recognition for their potential anti-cancer activity, cyclic peptides like Sansalvamide A, a marine-derived cyclic depsipeptide, have emerged as a potential anti-cancer agent due to their potent activity against various cancer types in preclinical studies. This review offers a comprehensive overview of Sansalvamide A, including its sources, structure-activity relationship, and semi-synthetic derivatives. The review also aims to outline the mechanisms through which Sansalvamide A and its analogs exert their anti-proliferative effects and to discuss the need for enhancements in pharmacokinetic profiles for better clinical utility. An extensive literature search was conducted, focusing on studies that detailed the anti-cancer activity of Sansalvamide A, its pharmacokinetics, and mechanistic pathways. Data from both in vitro and in vivo studies were collated and analyzed. Sansalvamide A and its analogs demonstrated significant anti-cancer activity across various cancer models, mediated through Hsp 90 inhibition, Topoisomerase inhibition, and G0/G1 cell cycle arrest. However, their pharmacokinetic properties were identified as a significant limitation, requiring improvement for effective clinical translation. Despite its notable anti-cancer effects, the utility of Sansalvamide A is currently limited by its pharmacokinetic characteristics. Therefore, while Sansalvamide A exhibits promise as an anti-cancer agent, there is a compelling need for further clinical and toxicological studies and optimization of its pharmacokinetic profile to fully exploit its therapeutic potential alongside modern cancer therapies.
随着基于肽的疗法因其潜在的抗癌活性而得到认可，海洋来源的环二肽 Sansalvamide A 等环状肽已成为一种有潜力的抗癌药物，因为在临床前研究中，它对各种癌症类型都具有很强的活性。
本综述全面介绍了 Sansalvamide A，包括其来源、结构-活性关系和半合成衍生物。综述还旨在概述 Sansalvamide A 及其类似物发挥抗增殖作用的机制，并讨论需要增强药代动力学特征以提高临床实用性。
进行了广泛的文献检索，重点关注详细描述 Sansalvamide A 的抗癌活性、药代动力学和机制途径的研究。收集和分析了来自体外和体内研究的数据。
Sansalvamide A 及其类似物在各种癌症模型中表现出显著的抗癌活性，这是通过 Hsp 90 抑制、拓扑异构酶抑制和 G0/G1 细胞周期停滞介导的。然而，它们的药代动力学特性被确定为一个重大限制，需要改进以实现有效的临床转化。
尽管 Sansalvamide A 具有显著的抗癌效果，但它的实用性目前受到药代动力学特征的限制。因此，虽然 Sansalvamide A 作为一种抗癌药物具有很大的应用前景，但仍需要进一步进行临床和毒理学研究，并优化其药代动力学特征，以充分发挥其与现代癌症治疗相结合的治疗潜力。
