Aryl amide compounds and uses thereof
By designing low-molecular-weight molecular glue degraders to enhance the interaction between Bcr-Abl T315I and E3 ligase, and utilizing the human protein degradation system, the problem of limited efficacy of traditional targeted kinase inhibitors against Bcr-Abl T315I mutants was solved, achieving highly efficient tumor cell inhibition and reduced drug resistance.
Patent Information
- Application Number
- CN202610540507.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-27
- Publication Date
- 2026-07-17
AI Technical Summary
Existing targeted kinase inhibitors have limited efficacy against Bcr-Abl T315I mutants, leading to high drug resistance. Traditional small molecule inhibitors cannot effectively degrade Bcr-Abl T315I kinase, affecting the treatment of tumors such as chronic myeloid leukemia.
A low molecular weight molecular glue degrader was designed and synthesized to promote the ubiquitination and degradation of Bcr-Abl T315I by enhancing the interaction between the target protein and E3 ligase, thereby achieving selective degradation of Bcr-Abl T315I by utilizing the protein degradation system in human cells.
It effectively inhibits the kinase activity of Bcr-Abl T315I mutant, significantly reduces the incidence of drug resistance mutations, has good anti-proliferative effects, few toxic side effects, excellent pharmacokinetic properties, and has potential for clinical application.
Smart Images
Figure CN122404327A_ABST