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E957-0282
- Development stage
- Preclinical
- Lead developer
- Beijing An Zhen Hospital
- Modality
- Small Molecules
01
Overview
E957-0282 is a small molecule atypical chemokine receptor 1 (ACKR1) inhibitor under development for the treatment of calcific aortic valve disease (CAVD). Identified using deep learning-based DeepDocking guided by the cryo-EM structure of ACKR1, E957-0282 exhibits nanomolar binding affinity to ACKR1. It acts by blocking the ACKR1-CXCL8 axis, which is upregulated in ACKR1-high valvular endothelial cells (VECs) during CAVD progression. By inhibiting ACKR1, E957-0282 prevents CXCL8-mediated endothelial-to-mesenchymal transition (EndoMT) and metabolic reprogramming (such as reduced fatty acid oxidation), thereby reducing valvular fibrosis and improving transvalvular hemodynamic outcomes.
02
Targets
ACKR1 (Atypical chemokine receptor 1)IL8 (C-X-C Motif Chemokine Ligand 8)
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