Sanglifehrin A mitigates multi-organ fibrosis by targeting the collagen chaperone cyclophilin B

Pathological deposition and crosslinking of collagen type I by activated myofibroblasts drives progressive tissue fibrosis. Therapies that inhibit collagen synthesis have potential as anti-fibrotic agents. We identify the collagen chaperone cyclophilin B as a major cellular target of the natural product sanglifehrin A (SfA) using photo-affinity labeling and chemical proteomics. Mechanistically, SfA inhibits and induces the secretion of cyclophilin B from the endoplasmic reticulum (ER) and prevents TGF-

• Flaxman, H. A.
• Chrysovergi, M. A.
• Han, H.
• Kabir, F.
• Lister, R. T.
• Chang, C. F.
• Yvon, R.
• Black, K. E.
• Weigert, A.
• Savai, R.
• Egea-Zorrilla, A.
• Pardo-Saganta, A.
• Lagares, D.
• Woo, C. M.