Synthetic Progress Towards a TMC-95 Analogue as a Potential Proteasome Inhibitor

  • M. Angels Estiarte
  • Amy M. Elder
  • Daniel H. Rich
Part of the American Peptide Symposia book series (APSY, volume 7)


Recently, four novel compounds, TMC 95A-D 1 (R1, R2 = H or OH; R3, R4 = H, OH or CH3), have been isolated from the fermentation broth of Apiospora montagnei Sacc. TC 1093 [1,2], and shown to inhibit the 20S proteasome (IC50 = 5.4–60 nM), an eukaryotic threonine protease responsible for the degradation of most cell proteins [3]. Increased levels of this enzyme and subsequent protein breakdown have been related to different diseases such as malaria, inflammation and cancer. Thus, inhibition of the proteasome is currently becoming a promising therapeutic target. In this work, we describe the synthetic approaches towards the synthesis of a novel indole analog 2 of the core of 1 to evaluate its possible activity as a proteasome inhibitor (Figure 1).


Fermentation Broth Proteasome Inhibitor Synthetic Approach Ring Size Indole Ring 
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Copyright information

© Springer Science+Business Media Dordrecht 2001

Authors and Affiliations

  • M. Angels Estiarte
    • 1
  • Amy M. Elder
    • 1
  • Daniel H. Rich
    • 1
  1. 1.Department of ChemistryUniversity of Wisconsin-MadisonMadisonUSA

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