Abstract
FKBP12 ligands such as FK506 have been shown to activate the BMP signaling pathway and facilitate tissue regeneration. However, the immunosuppressive activity of FK506 limits its clinical application. Using Heck reaction, we generated nonimmunosuppressive analogs of FK506 by fusing heterocycles to the calcineurin (CN) binding domain of FK506. Structure-activity relationships provided novel mechanistic insights into the FK506-CN interaction that can be exploited for rational design of future analogs.
Original language | English (US) |
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Pages (from-to) | 1279-1283 |
Number of pages | 5 |
Journal | ACS Medicinal Chemistry Letters |
Volume | 10 |
Issue number | 9 |
DOIs | |
State | Published - Sep 12 2019 |
Keywords
- BMP signaling
- FKBP ligands
- FKVP
- SMAD1/5
- calcineurin
- nonimmunosuppressive
- regenerative medicine
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry