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 IC 50 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.

Workflow management system is playing more and more significant role in business process management (BPM) and office automation (OA) of enterprises[. It can improve the efficiency and manageability of an enterprises daily teamwork, control as well as coordinate the processes[. Traditionally, it is not easy for the workflow modeling method to describe the complex business process clearly and intuitively. In this paper we improved the role based workflow model, and proposed a workflow modeling method based on multi-role playing. It is possible to make the modeling easier and simpler when we come to the complex business process modeling problems. Finally, an example of a B/S based Enterprise Financial Reimbursement Management System (EFRMS) is demonstrated to prove the convenience and feasibility about the method mentioned.