Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India.
Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India.
Pharmacol Ther. 2023 Oct;250:108525. doi: 10.1016/j.pharmthera.2023.108525. Epub 2023 Sep 9.
Cancer is one of the most common causes of death. So, its lethal effect increases with time. Near about hundreds of cancers are known in humans. Cancer treatment is done to cure or prolonged remission, and shrinkage of the tumor. Cytotoxic agents, biological agents/targeted drugs, hormonal drugs, surgery, radiotherapy/proton therapy, chemotherapy, immunotherapy, and gene therapy are currently used in the treatment of cancer but their cost is high and cause various side effects. Seeing this, some new targeted strategies such as PROTACs are the need of the time. Proteolysis targeting chimera (PROTAC) has become one of the most discussed topics regarding cancer treatment. Few of the PROTAC molecules are in the trial phases. PROTACs have many advantages over other strategies such as modularity, compatibility, sub-stoichiometric activity, acting on undruggable targets, molecular design, and acts on intracellular targets, selectivity and specificity can be recruited for any cancer, versatility, and others. PROTACs are having some unclear questions on their pharmacokinetics, heavy-molecular weight, etc. PROTACs are anticipated to bring about a conversion in current healthcare and will emerge as booming treatments. In this review article we summarize PROTACs, their mechanism of action, uses, advantages, disadvantages, challenges, and future aspects for the successful development of potent PROTACs as a drug strategy.
癌症是最常见的死亡原因之一。因此，它的致死效应随着时间的推移而增加。目前已知人类有近百种癌症。癌症的治疗目的是治愈或延长缓解期，并缩小肿瘤。细胞毒性药物、生物制剂/靶向药物、激素药物、手术、放疗/质子治疗、化疗、免疫疗法和基因疗法目前都用于癌症治疗，但它们的成本很高，且会引起各种副作用。鉴于此，一些新的靶向策略，如 PROTACs，是当前的需求。蛋白水解靶向嵌合体（PROTAC）已成为癌症治疗领域讨论最多的话题之一。一些 PROTAC 分子正在临床试验阶段。PROTACs 比其他策略具有许多优势，如模块化、兼容性、亚化学计量活性、针对不可成药靶点、分子设计以及针对细胞内靶点，可针对任何癌症招募选择性和特异性，多功能性等。PROTACs 在其药代动力学、分子量较大等方面存在一些不明确的问题。预计 PROTACs 将带来当前医疗保健的转变，并将成为热门的治疗方法。在这篇综述文章中，我们总结了 PROTACs 的作用机制、用途、优势、劣势、挑战和未来方面，以成功开发出有效的 PROTACs 作为药物策略。
