Polypeptide inhibitors targeting rna methyltransferase dimers and uses thereof
By designing the peptide inhibitor M14P1, which targets the METTL14 protein binding site, the translational assembly of the METTL3-METTL14 heterodimer was interfered with, thus solving the problems of drug resistance and significant side effects in existing AML treatments and achieving significant inhibition and apoptosis induction in AML cells.
Patent Information
- Application Number
- CN202510465001.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-15
- Publication Date
- 2026-07-24
- Estimated Expiration
- 2045-04-15
AI Technical Summary
Current treatments for acute myeloid leukemia (AML) suffer from high drug resistance and significant side effects. Furthermore, the overexpression of METTL3 and METTL14 plays a crucial role in the development and progression of leukemia and the regulation of chemotherapy response, and there is a lack of effective targeted therapies.
A peptide inhibitor, M14P1, targeting the METTL14 protein binding site was designed. It inhibits the activity of the METTL3-METTL14 heterodimer by interfering with its translational assembly. The specific amino acid sequence is RRRRRRRRGGGLDLGRVCLRKWGYRRCEDI, with the N-terminus fused with the R8 cell penetration peptide to enhance cell penetration.
It significantly inhibits the proliferation and survival of AML cells, reduces the m6A level of poly(A)RNA, induces AML cell apoptosis, and reduces the expression of AML-related proteins, showing unique anti-leukemia activity.