WF14861, a new cathepsins B and L inhibitor produced by Colletotrichum sp. II. Biological properties.
WF14861, 3-(N-(1-(N-(4-aminobutyl)-N-(3-aminopropyl)carbamoyl)-2-(4-hydroxyphenyl )ethyl)carbamoyl)oxirane-2-carboxylic acid, was obtained from the culture mycelium of Colletotrichum sp. as a novel cathepsins B and L inhibitor. WF14861 also showed inhibitory activities against bone derived crude protease and other cysteine proteases in vitro. The compound ameliorated the tissue damage and the bone destruction models of low-calcium-diet-fed mouse and adjuvant arthritis rat model.
Otsuka
T
T
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan.
Muramatsu
Y
Y
Niikura
K
K
Okamoto
M
M
Hino
M
M
Hashimoto
S
S
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy; D001862:Bone Resorption / Q000209:etiology / Q000517:prevention & control; D001842:Bone and Bones / Q000201:enzymology; D002136:Calcium, Dietary / Q000008:administration & dosage; D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D002642:Chick Embryo; D020231:Colletotrichum / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D010450:Endopeptidases; D004852:Epoxy Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D051379:Mice; D051381:Rats; D011917:Rats, Inbred Lew; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D002136:Calcium, Dietary; D015853:Cysteine Proteinase Inhibitors; D004852:Epoxy Compounds; C121124:WF 14861; D014443:Tyrosine; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C534280:Ctsl protein, rat