Timcodar (VX-853) Is a Non-FKBP12 Binding Macrolide Derivative That Inhibits PPAR γ and Suppresses Adipogenesis

Terry D. Hinds, Kezia John, Lucien McBeth, Christopher J. Trabbic, Edwin R. Sanchez

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Nutrient overload and genetic factors have led to a worldwide epidemic of obesity that is the underlying cause of diabetes, atherosclerosis, and cardiovascular disease. In this study, we used macrolide drugs such as FK506, rapamycin, and macrolide derived, timcodar (VX-853), to determine their effects on lipid accumulation during adipogenesis. Rapamycin and FK506 bind to FK506-binding proteins (FKBPs), such as FKBP12, which causes suppression of the immune system and inhibition of mTOR. Rapamycin has been previously reported to inhibit the adipogenic process and lipid accumulation. However, rapamycin treatment in rodents caused immune suppression and glucose resistance, even though the mice lost weight. Here we show that timcodar (1 μM), a non-FKBP12-binding drug, significantly (p < 0.001) inhibited lipid accumulation during adipogenesis. A comparison of the same concentration of timcodar (1 μM) and rapamycin (1 μM) showed that both are inhibitors of lipid accumulation during adipogenesis. Importantly, timcodar potently (p < 0.01) suppressed transcriptional regulators of adipogenesis, PPARγ and C/EBP, resulting in the inhibition of genes involved in lipid accumulation. These studies set the stage for timcodar as a possible antiobesity therapy, which is rapidly emerging as a pandemic.

Original languageEnglish
Article number6218637
JournalPPAR Research
StatePublished - 2016

Bibliographical note

Publisher Copyright:
© 2016 Terry D. Hinds Jr. et al.

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology (medical)


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