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What Is Geldanamycin?

By Jillian O Keeffe
Updated May 17, 2024
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Geldanamycin is an antibiotic drug, that is quite toxic to human beings. This drug does appear to be beneficial in preventing growth of some infectious organisms, and it may play a useful role in the treatment of other medical conditions. Researchers in the field of cancer treatment think that the specific action of the drug in the body may help to treat tumor growth. Due to the intrinsic toxicity of geldanamycin, synthetic copies with a few tweaks have been produced for research purposes.

First discovered in 1970, geldanamycin is a natural product of a bacterial species called Streptococcus hygroscopicus. Through scientific studies on the molecule, scientists found that the substance could have a beneficial effect on viral replication. Herpes simplex virus is one such infectious organism that geldanamycin exhibits antibiotic activity against.

Research has also figured out how the substance acts inside the body, which made the substance an attractive drug for other conditions. It acts directly on a molecule called heat shock protein 90 (Hsp90,) to block it from doing its normal job. This protein is very common in the body, and it acts as a guardian for a variety of other molecules. Some of these other molecules are involved in cell growth and replication, a process which is integral to both tumor cells and viral infections like herpes simplex.

Blocking this protein therefore reduces viral replication, as viruses need to hijack host cell machinery to help the viral particle reproduce itself. Compared to antibiotics used to combat bacteria or fungi, few antibiotics that target viruses are available. It can also potentially prevent the replication of cancer cells, as the molecules driving replication are not helped to do so by hsp-90. The major problem with geldanamycin itself for medical researchers is that it is very toxic to humans, and can seriously damage the liver. It also does not dissolve in water, which presents complications for making injections and other liquid drug products.

Instead of concentrating on geldanamycin alone, scientists decided to make synthetic copies of the molecule with minor tweaks to the structure. These little tweaks tend to be differences in the part of the molecule known as the 17-substituent, and commonly, the synthetic analogs have names that relate to the type of tweak present at that 17-substituent, such as 17-allylamino-demethoxygeldamycin (17-AAG) for example. As of 2011, research is ongoing into the effectiveness of these drugs against tumors or viral infections.

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