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The novel gluconeogenesis inhibitor FR225654, isolated from the culture broth of Phoma sp. No. 00144, has an unique structure that consists of a highly oxygenated trans-decalin ring and a beta-keto-enol, with a characteristic side chain. This compound selectively inhibited gluconeogenesis of rat primary hepatocytes and had hypoglycemic effects in several in vivo mouse models.

A novel gluconeogenesis inhibitor, FR225654 was isolated from the culture broth of Phoma sp. No. 00144. Spectroscopic analysis concluded that FR225654 has a highly oxygenated trans-decalin ring and beta-keto-enol in its main part, and has a characteristic side chain possessing a conjugated carboxylic acid and tri-substituted olefin.

FR225654, a novel gluconeogenesis inhibitor, was isolated from the culture broth of Phoma sp. No. 00144 and purified by adsorptive resin and reverse-phase column chromatography. This compound is a potent inhibitor of gluconeogenesis and is a promising candidate of anti-diabetic agent.

FR225659 was originally isolated as a novel gluconeogenesis inhibitor produced by fungal strain Helicomyces sp. No. 19353. To identify the target protein of FR225659, we synthesized high-performance affinity latex beads that immobilized FR225659 derivative FR253761 or FR259383. Using these beads, we identified FR225659 binding proteins as serine/threonine protein phosphatase type1 (PP1) and type2A (PP2A) from rat hepatocyte crude extract. FR225659 and its synthetic derivatives were strongly inhibited the enzyme activities of purified catalytic subunits of PP1 and PP2A in vitro.

FR171456 and FR173945, novel and potent cholesterol synthesis inhibitors, have been isolated from the fermentation broth of a fungal strain No. 15604. This strain was identified Sporormiella minima from its mycological characteristics. FR171456 and FR173945 strongly inhibited cholesterol synthesis in human hepatoma cell line Hep G2. These compounds also have in vitro antifungal activity against Candida albicans and Aspergillus fumigatus.

FR225659 and four related compounds are novel gluconeogenesis inhibitors that consist of a novel acyl-group and three abnormal amino acids. They were isolated from the culture broth of Helicomyces sp. No. 19353 and can be purified by absorptive resin and reverse-phase column chromatography. They are potent inhibitors of gluconeogenesis in primary cultured rat hepatocytes and thus may be useful as anti-diabetic agents.

The novel gluconeogenesis inhibitor FR225659 and four related compounds were isolated from the cultured broth of a fungal strain No. 19353. These compounds inhibited the glucagon-stimulated gluconeogenesis of rat primary hepatocytes and had hypoglycemic effects in two different in vivo models.

During the course of screening for novel gluconeogenesis inhibitors, FR225659 and its related compounds were isolated from a fermentation broth of Helicomyces sp. No. 19353. Spectroscopic analysis concluded that FR225659 is an N-acyl tripeptide consisting of a novel acyl, a 3-chloro-4-hydroxyarginine, a 3-hydroxy-3-methylproline and a dehydrovaline. Degradation study allowed assignment of the absolute configuration of the 3-hydroxy-3-methylproline to be (2S,3R). FR225656 was shown to possess a dehydroisoleucine instead of the dehydrovaline of FR225659.