One-step Heck Reaction Generates Nonimmunosuppressive FK506 Analogs for Pharmacological BMP Activation

Yuefan Wang, Brandon J. Peiffer, Qi Su, Jun Liu

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1279-1283
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume10
Issue number9
DOIs
StatePublished - Sep 12 2019

Fingerprint

Tacrolimus
Chemical activation
Pharmacology
Calcineurin
Tacrolimus Binding Protein 1A
Tissue regeneration
Structure-Activity Relationship
Immunosuppressive Agents
Regeneration
Ligands

Keywords

  • BMP signaling
  • calcineurin
  • FKBP ligands
  • FKVP
  • nonimmunosuppressive
  • regenerative medicine
  • SMAD1/5

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

One-step Heck Reaction Generates Nonimmunosuppressive FK506 Analogs for Pharmacological BMP Activation. / Wang, Yuefan; Peiffer, Brandon J.; Su, Qi; Liu, Jun.

In: ACS Medicinal Chemistry Letters, Vol. 10, No. 9, 12.09.2019, p. 1279-1283.

Research output: Contribution to journalArticle

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