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COL1A2-pep1
- Development stage
- Preclinical
- Lead developer
- Shanghai Chest Hospital
- Modality
- Peptides
- Administration
- Subcutaneous
01
Overview
COL1A2-pep1 is an extracellular matrix (ECM)-derived exerkine (exercise-induced small peptide) being developed by Shanghai Chest Hospital for the prevention and treatment of pathological cardiac remodeling, including cardiac hypertrophy and fibrosis. It was identified via human plasma peptidomics screening of individuals undergoing regular exercise. Mechanistically, COL1A2-pep1 directly binds to the catalytic domain of the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS), inhibiting its activation and the downstream STING-IRF3-mediated inflammatory cascade. This targeted inhibition of cGAS restores ATP production in cardiomyocytes and activates the PINK1/Parkin signaling pathway, enhancing mitophagy flux, clearing damaged mitochondria, and preventing cytosolic mitochondrial DNA (mtDNA) leakage.
02
Targets
Cyclic GMP–AMP synthasePINK1 (PTEN-induced kinase 1)PRKN (E3 ubiquitin-protein ligase parkin)STING (Stimulator of interferon genes protein)
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