State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
Eur J Med Chem. 2023 Nov 5;259:115702. doi: 10.1016/j.ejmech.2023.115702. Epub 2023 Aug 1.
Tuberculosis (TB) is one of the most threatening diseases for humans, however, the drug treatment strategy for TB has been stagnant and inadequate, which could not meet current treatment needs. TB is caused by Mycobacterial tuberculosis, which has a unique cell wall that plays a crucial role in its growth, virulence, and drug resistance. Polyketide synthase 13 (Pks13) is an essential enzyme that catalyzes the biosynthesis of the cell wall and its critical role is only found in Mycobacteria. Therefore, Pks13 is a promising target for developing novel anti-TB drugs. In this review, we first introduced the mechanism of targeting Pks13 for TB treatment. Subsequently, we focused on summarizing the recent advance of Pks13 inhibitors, including the challenges encountered during their discovery and the rational design strategies employed to overcome these obstacles, which could be helpful for the development of novel Pks13 inhibitors in the future.
结核病（TB）是对人类最具威胁的疾病之一，然而，结核病的药物治疗策略一直停滞不前，无法满足当前的治疗需求。结核病是由结核分枝杆菌引起的，它具有独特的细胞壁，在其生长、毒力和耐药性方面发挥着关键作用。聚酮合酶 13（Pks13）是一种必需的酶，它催化细胞壁的生物合成，其关键作用仅在分枝杆菌中发现。因此，Pks13 是开发新型抗结核药物的有前途的靶标。在这篇综述中，我们首先介绍了针对 Pks13 治疗结核病的机制。随后，我们重点总结了 Pks13 抑制剂的最新进展，包括在发现过程中遇到的挑战以及为克服这些障碍而采用的合理设计策略，这有助于未来开发新型 Pks13 抑制剂。
