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Updated: Jul 19, 2025
Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
Published on: November 22, 2024
Facilitated Drug Repurposing with Artemisinin-Derived PROTACs: Unveiling PCLAF as a Therapeutic Target
Yan Li1, Zi Wei Zeng1, Di Chen1
1State Key Laboratory of Functions and Applications of Medicinal, Plants Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, School of Basic Medical Science, Guizhou Medical University, Guiyang 550004, China.
Abstract:
Artemisinin, a prominent anti-malaria drug, is being investigated for its potential as a repurposed cancer treatment. However, its effectiveness in tumor cell lines remains limited, and its mechanism of action is unclear. To make more progress, the PROteolysis-TArgeting chimera (PROTAC) technique has been applied to design and synthesize novel artemisinin derivatives in this study. Among them, AD4, the most potent compound, exhibited an IC50 value of 50.6 nM in RS4;11 cells, over 12-fold better than that of its parent compound, SM1044. This was supported by prolonged survival of RS4;11-transplanted NOD/SCID mice. Meanwhile, AD4 effectively degraded PCLAF in RS4;11 cells and thus activated the p21/Rb axis to exert antitumor activity by directly targeting PCLAF. The discovery of AD4 highlights the great potential of using PROTACs to improve the efficacy of natural products, identify therapeutic targets, and facilitate drug repurposing. This opens a promising avenue for transforming other natural products into effective therapies.
