Preclinical study demonstrates antitumor activity and Cdc25A/B inhibition by TMC-69-6H in murine cancer models, highlighting its therapeutic potential.
A new antibiotic designated TMC-69has been isolated from,the fermentation broth of a fungal strain Chrysosporium sp.TC 1068.TMC-69exhibited moderate in vitro cytotoxic activity.TMC-69-6H, a derivative of TMC-69prepared by hydrogenation, possessed more potent in vitro cytotoxicity than TMC-69, and exhibited in vivo antitumor activity against murine P388 leukemia and B16 melanoma.TMC-69-6H was found to specifically inhibit Cdc25Aand B phosphatases.In the course of our screening program aimed at new antitumor substances from microorganisms, we isolated new cytotoxic antibiotics, TMC-1and TMC-135 A and B from Streptomyces sp.strains1^, TMC-151 A~F, TMC-154, and TMC-171A~Cfrom Gliocladium sp.strains3'4), and TMC-1 69 from Aspergillusflavipes5)'.Further screening has resulted in isolation of a unique active metabolite named TMC-69 (Fig. 1) from the culture broth of a fungus identified as Chrysosporium sp.TC 1068.Hexahydro-
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Hirano et al. (2001) studied this question.
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