345805

Geldanamycin, Streptomyces hygroscopicus

A benzoquinoid antibiotic that inhibits p60^c-src tyrosine kinase and c-myc gene expression in murine lymphoblastoma cells.

• Synonym(s): Geldanamycin, Streptomyces hygroscopicus
• Empirical Formula (Hill Notation): C₂₉H₄₀N₂O₉
• CAS Number: 30562-34-6
• Molecular Weight: 560.64
• MDL number: MFCD00274570
• UNSPSC Code: 12352200

Properties

• Quality Level: 100
• Assay: ≥95% (HPLC)
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: yellow
• solubility: DMSO: 1 mg/mL
• shipped in: ambient
• storage temp.: −20°C
• InChI: 1S/C29H40N2O9/c1-15-11-19-25(34)20(14-21(32)27(19)39-7)31-28(35)16(2)9-8-10-22(37-5)26(40-29(30)36)18(4)13-17(3)24(33)23(12-15)38-6/h8-10,13-15,17,22-24,26,33H,11-12H2,1-7H3,(H2,30,36)(H,31,35)/b10-8-,16-9+,18-13+/t15-,17+,22+,23+,24-,26+/m1/s1
• InChI key: QTQAWLPCGQOSGP-KSRBKZBZSA-N

Description

General description

A benzoquinoid antibiotic that inhibits p60^c-src tyrosine kinase and c-myc gene expression in murine lymphoblastoma cells. Geldanamycin has antiproliferative and antitumor effects. Rapidly depletes p185^c-erbB2 protein tyrosine kinase in breast carcinoma cells. Binds to HSP90 and disrupts Raf1-HSP90 complex leading to destabilization of Raf1. Inhibits basal and hypoxia-induced expression of c-Jun (IC₅₀ = 75 nM) and abolishes hypoxia-induced increase in c-Jun N-terminal kinase activity. Also known to selectively destabilize mutated p53 protein from a number of breast, leukemia, and prostate cell lines.

A benzoquinoid antibiotic that is a potent inhibitor of pp60^src tyrosine kinase. Geldanamycin has antiproliferative and antitumor effects. Inhibits basal and hypoxia-induced expression of c-Jun (IC₅₀ = 75 nM) and abolishes hypoxia-induced increase in c-Jun N-terminal Kinase activity. Binds to HSP90 and disrupts raf1-HSP90 complex leading to destabilizing of Raf1. Also destabilizes mutant p53 protein from a number of breast, leukemic, and prostate cell lines. Inhibits c-myc expression in murine lymphoblastoma cells. Approximately ten-fold more potent than herbimycin A (Cat. No. 375670).

Biochem/physiol Actions

Cell permeable: no

Primary Target
pc60^c-svc tyrosine kinase

Product does not compete with ATP.

Reversible: no

Target IC₅₀: 75 nM Inhibiting basal and hypoxia-induced expression of c-Jun

Warning

Toxicity: Standard Handling (A)

Preparation Note

Further dilute with aqueous buffers just prior to use.

Other Notes

Vasilevskaya, I.A., and O’Dwyer, P.J. 1999. Cancer Res.59, 3935.
Mimnaugh, E.G., et al. 1996. J. Biol. Chem. 271, 22796.
Schulte, T.W., et al. 1996. Mol. Cell. Biol. 16, 5839.
Blagosklonny, M.V., et al. 1995. Oncogene11, 933.
Schnur, R.C., et al. 1995. J. Med. Chem.38, 3806.
Whitesell, L., et all. 1994. Proc. Natl. Acad. USA91, 8324.
Yamaki, H., et al. 1989. J. Antibiot.42, 604.
Uehara, Y., et al. 1984. Mol. Cell. Biol.6, 2198.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 2
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable