Derrubone, an inhibitor of the Hsp90 protein folding machinery.
High-throughput screening of a library of diverse molecules has identified derrubone ( 1), an isoflavone natural product from Derris robusta, as a potent Hsp90 inhibitor. Subsequent testing in several cellular-based assays established 1 as a low micromolar inhibitor in vitro. In addition, derrubone induced the degradation of numerous Hsp90 client proteins, a hallmark effect resulting from Hsp90 inhibition. The identification of 1 as an Hsp90 inhibitor provides a new natural product scaffold upon which the development of novel Hsp90 inhibitors can be pursued.
Hadden
M Kyle
MK
Department of Medicinal Chemistry, Malott 4070, The University of Kansas, Lawrence, KS 66045-7563, USA.
Galam
Lakshmi
L
Gestwicki
Jason E
JE
Matts
Robert L
RL
Blagg
Brian S J
BS
D000818:Animals; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D049409:Luciferases, Firefly / Q000378:metabolism*; D015394:Molecular Structure; D017510:Protein Folding; D011817:Rabbits; D012156:Reticulocytes / Q000187:drug effects
D018841:HSP90 Heat-Shock Proteins; D007529:Isoflavones; C527020:derrubone; D049409:Luciferases, Firefly