Structure of Tyroscherin, an Antitumor Antibiotic against IGF-1-dependent Cells from Pseudallescheria sp.

The Journal of Antibiotics
2004.0

Abstract

Insulin-like growth factors (IGFs) play a key role in human cancer progression1). IGF signals through IGF-1 receptor are known to be significant for tumor cell growth and survival. Thus, selective inhibitors of IGF signal transduction are expected to be new anticancer agents against IGF-dependent tumor cells. In the course of our screening for inhibitors of IGF-dependent cell growth or survival, a fungal strain identified as Pseudallescheria sp. was found to produce an active substance designated tyroscherin (Fig. 1). An antitumor antibiotic, tyroscherin, was isolated from the culture of a fungus identified as Pseudallescheria sp. The structure of tyroscherin including the absolute stereochemistry was determined as shown in Fig. 1 by NMR and degradation studies. Tyroscherin selectively inhibited IGF-1-dependent growth of MCF-7 human breast cancer cells with an IC50 of 9.7ng/ml.

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