PROTAC chimera for targeted degradation of ALKBH5 as well as preparation method and application of PROTAC chimera
By designing the PROTAC chimera, using the ALKBH5 targeting ligand and E3 ubiquitin ligase to recruit the ligand, and binding it to a flexible polyethylene glycol chain, the irreversible degradation of the ALKBH5 protein is achieved. This overcomes the limitations of existing small molecule inhibitors, significantly inhibits tumor cell proliferation and reverses chemotherapy resistance, and provides an efficient and selective targeted degradation strategy.
Patent Information
- Application Number
- CN202610400076.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-03-30
- Publication Date
- 2026-07-10
AI Technical Summary
Existing small molecule inhibitors targeting ALKBH5 cannot completely eliminate the ALKBH5 protein in cells, easily leading to compensatory upregulation of the target protein and drug resistance. There is a lack of efficient and selective targeted degradation strategies.
A novel PROTAC chimera was designed, employing an ALKBH5 targeting ligand, an E3 ubiquitin ligase to recruit the ligand, and a flexible polyethylene glycol chain. Irreversible degradation of the ALKBH5 protein was achieved through ubiquitination modification, and the complete clearance of the target protein was mediated by the catalytic properties of the PROTAC molecule and the proteasome system.
It achieves complete clearance of ALKBH5 protein, overcomes the limitations of traditional inhibitors, significantly inhibits tumor cell proliferation, reverses chemotherapy resistance, and has highly selective and long-lasting targeted degradation effects, reducing drug dosage and off-target toxicity.