Geldanamycin Chemical Properties

Melting point:

255 °C

Boiling point:

627.87°C (rough estimate)

Density 

1.2443 (rough estimate)

refractive index 

1.5800 (estimate)

Flash point:

87℃

storage temp. 

-20°C

solubility 

DMSO: soluble

form 

powder

pka

8.42±0.70(Predicted)

color 

yellow to orange

λmax

305nm(MeOH)(lit.)

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months

CAS DataBase Reference

30562-34-6(CAS DataBase Reference)

Safety Information

Hazard Codes 

T,Xi

Risk Statements 

36/37/38

Safety Statements 

26-27-36/37/39-24/25

WGK Germany 

2

RTECS 

LX8920000

HS Code 

29419090

MSDS

• Language:English Provider:SigmaAldrich

Geldanamycin Usage And Synthesis

Description

Geldanamycin from Streptomyces hygroscopicus.
Geldanamycin is a benzoquinone ansamycin antitumor antibiotic. Geldanamycin binds specifically to Hsp90 (Heat Shock Protein 90) and to its endoplasmic reticulum homologue GP96. The Hsp90 chaperone is required for the activation of several families of eukaryotic protein kinases and nuclear hormone receptors, many of which are proto-oncogenic and play a prominent role in cancer. The geldanamycin antibiotic has antiproliferative and antitumor effects, as it binds to Hsp90, inhibits the Hsp90-mediated conformational maturation/refolding reaction, and results in the degradation of Hsp90 substrates. Hsp90 also plays a key role in regulating the physiology of cells exposed to environmental stress and thus, geldanamycin interferes with cellular stress response.
Geldanamycin was found to be a potent antibiotic active at nanomolar concentrations against 60 cell lines as well as in mouse tumor models.
It is an inhibitor of proto-oncogenic protein kinases, such as erbB22, EFG receptor tyrosine kinases, and non-receptor tyrosine kinases, such as v-src and Raf-1. In addition, it is a potent inhibitor of the nuclear hormone receptor family including the estrogen and androgen hormone receptors.

Description

Geldanamycin is a benzoquinone ansamycin antibiotic which binds heat shock protein 90 (Hsp90) and its paralog GRP94, altering their actions. Through its interaction with these chaperones, geldanamycin indirectly affects numerous client proteins with roles in diverse cellular processes, including gene expression, cell proliferation, apoptosis, and angiogenesis. For example, geldanamycin inhibits c-jun expression in human colon adenocarcinoma HT29 cells (IC₅₀ = 75 nM), inhibiting AP-1 binding. It also reduces signaling through mitogenic signaling proteins and interferes with steroid receptor function. Inhibitors of Hsp90, including geldanamycin, show promise in cancer therapy.

Chemical Properties

Yellow to Orange Powder

Uses

Geldanamycin is a potent antitumor antibiotic active at nanomolar concentration against 60 cell lines. It binds specifically to the heat shock protein Hsp90 and to its endoplasmic reticulum homologue GP96, and thus interferes with conformational maturation of proteins and the cellular stress response. In addition, it is a potent inhibitor of the nuclear hormone receptor family.

Uses

Geldanamycin is benzoquinone ansamycin antibiotic isolated from Streptomyces hygroscopicus. It is a potent antitumour metabolite that acts by binding to the 90-kDa heat-shock protein (Hsp90) essential to maintain the conformation, stability, activity and cellular localisation of several key oncogenic proteins such as ERBB2, C-RAF, CDK4, AKT/PKB, steroid hormone receptors, mutant p53, HIF-1α, survivin and telomerase hTERT.

Uses

Geldanamycin?binds to and inhibits the cytosolic chaperone functions of heat shock protein 90 (HSP90). HSP90 maintains the stability and functional shape of many oncogenic signaling proteins. It interferes with conformational maturation of proteins and the cellular stress response. In addition, it is a potent inhibitor of the nuclear hormone receptor family.

Definition

ChEBI: An ansamycin consisting of a 19-membered macrocyle incorporating a benzoquinone ring and a lactam functionality. It shows antimicrobial activity against many Gram-positive and some Gram-negative bacteria.

General Description

Chemical structure: benzenoid

Biological Activity

Selectively inhibits heat shock protein 90 (Hsp90). Binds to the ATP site of Hsp90 (K d = 1.2 μ M) and inhibits its chaperone activity. Consequently inhibits activities of oncogenic kinases (e.g. src, Raf), p53 and steroid receptors.

Biochem/physiol Actions

Primary Targetpc60c-svc tyrosine kinase

storage

+4°C

References

1) Neckers et al. (1999), Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity; Invest. New Drugs, 17 361 2) Zang et al. (2006), HSP90 protects apoptotic cleavage of vimentin in geldanamycin-induced apoptosis; Mol. Cell. Biochem., 281 111

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