WF14865A and B, new cathepsins B and L inhibitors produced by Aphanoascus fulvescens. I. Taxonomy, production, purification and biological properties.

T Otsuka, Y Muramatsu, T Nakanishi, H Hatanaka, M Okamoto, M Hino, S Hashimoto

Exploratory Research Laboratories, Fujisawa Pharmaceutical Co, Ltd, Tsukuba, Ibaraki, Japan.

The Journal of antibiotics 2000 May

filter terms:

WF14865A and B, novel cathepsins B and L inhibitors, were produced and isolated separately from the culture mycelium of a fungal strain Aphanoascus fulvescens No. 14865. Spectroscopic analysis revealed that both WF14865A and B were composed of trans-epoxysuccinyl moieties, 1-H-imidazole-2-ylamine, and isoleucine or leucine. These compounds inhibited human cathepsins B and L with IC50 values in the range of 8.4 approximately 72nM in vitro. Though their in vitro properties were typical as trans-epoxysuccinyl type inhibitors, they exerted strong bone resorption inhibitory effects in low-calcium-diet-fed mouse model at 3.2 approximately 10 mg/kg.

Citation

T Otsuka, Y Muramatsu, T Nakanishi, H Hatanaka, M Okamoto, M Hino, S Hashimoto. WF14865A and B, new cathepsins B and L inhibitors produced by Aphanoascus fulvescens. I. Taxonomy, production, purification and biological properties. The Journal of antibiotics. 2000 May;53(5):449-58