Identification of small molecule chemical inhibitors of the collagen-specific chaperone Hsp47.
Hsp47 is a collagen-specific molecular chaperone whose activity has been implicated in the pathogenesis of fibrotic diseases. Here, we describe the development of an assay for screening libraries of chemical compounds for inhibitors of Hsp47. A preliminary screen of 2080 compounds identified four that demonstrated inhibitory activity against Hsp47 in vitro, with IC(50) values ranging from 3 to 27 muM. Compounds identified through this method may provide the basis for development of novel antifibrotic therapeutics.
Thomson
Christy A
CA
Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. christy@brc.ubc.ca
Atkinson
Helen M
HM
Ananthanarayanan
Vettai S
VS
D003094:Collagen / Q000378:metabolism*; D016208:Databases, Factual; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D009391:Nephelometry and Turbidimetry; D011724:Pyridazines / Q000737:chemistry; D015843:Serpins / Q000737:chemistry* / Q000378:metabolism; D013440:Sulfides / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry; D013876:Thiophenes / Q000737:chemistry
D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011724:Pyridazines; D015843:Serpins; D013440:Sulfides; D013844:Thiazoles; D013876:Thiophenes; D003094:Collagen