references about GELDANAMYCIN

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Geldanamycin (GA) is a naturally-occurring drug produced by microorganisms to protect themselves from disease-causing substances. GA binds to a special kind of protein called a heat shock protein. All cells produce a common set of heat shock proteins (Hsp’s) in response to a variety of stresses, including heat, exposure to toxic compounds, or other conditions that cells normally do not experience. Experiments with bacteria, yeast, fruit flies, and mice have shown that increased production of heat shock proteins can protect an organism against stress-induced damage. There are many different kinds of heat shock proteins – each one of them performs a variety of functions that help the cell in both stressful and non-stressful conditions. Most, but not all, heat shock proteins play the role of “molecular chaperones.” Molecular chaperones are substances inside the cell that bind and stabilize proteins at intermediate stages of folding, assembly, movement across membranes, and degradation.

Geldanamycin has been shown  preventing huntingtin aggregation.

First of all, it would be helpful to understand how GA works as an anti-tumor drug because its mode of action against cancer and huntingtin aggregation is similar. In other research, scientists have shown that GA binds to the heat shock protein Hsp 90, which acts as a molecular chaperone. Some of the proteins that Hsp 90 chaperones are proteins involved in the progression of cancer. But once GA binds to Hsp 90, Hsp 90 loses its ability to act as a chaperone. Because Hsp 90 is then unable to help the cancer-causing proteins fold properly, these proteins end up being malformed. Cells in the human body continually degrade improperly folded proteins, so the end result of the loss of function of Hsp 90 is the degradation of proteins involved in the progression of cancer.

LD50 : 400 mg / kg 

([18S- (4E,5Z,8R*,9R*,10E,12R*,13S*,14R*,16S*)]- 9- [(aminocarbonyl)oxy]- 13- hydroxy- 8,14,19- trimetoxy- 4,10,12,16- tetramethyl- 2- azabicyclo[16.3.1.]docosa- 4,6,10,18,21- pentan- 3,20,22trion 



HSP90 in Complex with Geldanamycin (yellow)










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