DR3penA

DR3penA is a novel hydrocarbon-stapled peptide developed for the treatment of renal fibrosis and chronic kidney disease. Developed by researchers at Sun Yat-sen University, the peptide is a mimetic of the Smad-binding domain of the BMP and activin membrane-bound inhibitor (BAMBI), featuring the sequence DHα-(4-pentenyl)-AlaNPQIR-NH2. The hydrocarbon staple enhances the peptide's stability and pharmacological properties compared to its linear counterparts. DR3penA acts as a potent inhibitor of the Transforming Growth Factor-beta 1 (TGF-β1) signaling pathway, a central driver of fibrotic processes. Its mechanism involves the modulation of the miR-212-5p/LDLRAD4 axis; specifically, it represses TGF-β1 signaling by promoting miR-212-5p-mediated targeting of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4), which in turn prevents the activation of Smad2 and Smad3. In preclinical mouse models of unilateral ureteral obstruction (UUO) and cisplatin-induced kidney injury, DR3penA demonstrated the ability to preserve renal function and reduce existing fibrosis at doses significantly lower than conventional therapies like captopril, while maintaining a low toxicity profile.

Other names

DHα-(4-pentenyl)-AlaNPQIR-NH2