Facilitated Drug Repurposing with Artemisinin-Derived PROTACs: Unveiling PCLAF as a Therapeutic Target.

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.

[Effects of different water potentials on leaf gas exchange and chlorophyll fluorescence parameters of cucumber during post-flowering growth stage].

Impacts of different substrate water potentials (SWP) on leaf gas exchange and chlorophyll fluorescence parameters of greenhouse cucumber during its post-flowering growth stage were analyzed in this study. The results demonstrated that -10 and -30 kPa were the critical values for initiating stomatal and non-stomatal limitation of drought stress, respectively. During the stage of no drought stress (-10 kPa < SWP ≤ 0 kPa), gas exchange parameters and chlorophyll fluorescence parameters were not different significantly among treatments. During the stage of stomatal limitation of drought stress (-30 kPa