ICM0201, a New Inhibitor of Osteoclastogenesis from Cunninghamella sp. F-1490. I. Taxonomy, Fermentation, Isolation and Biological Activities.

The Journal of Antibiotics
2003.0

Abstract

In the course of screening for inhibitors of osteoclastogenesis, a new substance designated as ICM0201 was isolated from a fermentation broth of Cunninghamella sp. F-1490. Because the inhibition of bone resorption is a primary therapeutic objective, we have established in vitro screening system for natural products that inhibit osteoclastogenesis. We have searched for substances that inhibit osteoclastogenesis in mouse bone marrow cell cultures using PTHrP as inducer of osteoclastogenesis and TRAP activity expression as an index of osteoclast formation. As a result, we have isolated ICM0201 from a culture filtrate of fungal strain F-1490. ICM0201 inhibited the formation of osteoclasts in mouse bone marrow cells with an IC50 value of 0.78μg/ml and showed weak cytotoxicity against bone marrow cells. ICM0201 inhibited PTHrP-induced pit-formation without significant cytotoxicity and showed no cytotoxicity against mouse tumor cell lines such as L-1210, Colon 26 and B16BL6 with IC50 value over 100μg/ml. In this paper, we describe the taxonomy of the producing strain, fermentation, isolation and biological activities of ICM0201.

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