Kurian Ritika, Wang Hongbing
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, MD 21201, USA.
Int J Mol Sci. 2025 Jan 24;26(3):988. doi: 10.3390/ijms26030988.
A prodrug is a molecule that lacks pharmacological activity, but upon enzymatic bioactivation, it can generate a therapeutically active molecule. The primary reason behind the design of a prodrug is to help circumvent challenges associated with the physicochemical properties of a drug molecule, such as solubility, absorption, distribution, and instability. Chemotherapy has been at the forefront of cancer treatment for over 70 years due to its ability to target rapidly proliferating tumor cells. However, a major concern with conventional chemotherapy is the lack of selectivity and its associated side toxicity, which can severely impact patients' quality of life. In oncology, prodrugs have been explored to enhance the bioavailability, improve efficacy, and minimize systemic toxicity of chemotherapeutic agents. Prodrugs activated by enzymes unique to a tumor microenvironment can significantly increase targeted delivery of chemotherapeutic drugs. This review aims to highlight commonly used chemotherapeutic prodrugs, including both alkylating and non-alkylating agents, and discuss their clinical relevance, mechanisms of bioactivation, and toxicity concerns.
前药是一种缺乏药理活性的分子，但在酶促生物活化后，它可以产生具有治疗活性的分子。设计前药的主要原因是帮助克服与药物分子物理化学性质相关的挑战，如溶解度、吸收、分布和不稳定性。由于化疗能够靶向快速增殖的肿瘤细胞，在过去70多年里一直处于癌症治疗的前沿。然而，传统化疗的一个主要问题是缺乏选择性及其相关的副作用毒性，这可能严重影响患者的生活质量。在肿瘤学中，人们一直在探索前药以提高化疗药物的生物利用度、改善疗效并将全身毒性降至最低。由肿瘤微环境特有的酶激活的前药可以显著增加化疗药物的靶向递送。本综述旨在突出常用的化疗前药，包括烷基化剂和非烷基化剂，并讨论它们的临床相关性、生物活化机制和毒性问题。
