| Identification | More | [Name]
Geldanamycin | [CAS]
30562-34-6 | [Synonyms]
9,13-DIHYDROXY-8,14,19-TRIMETHOXY-4,10,12,16-TETRAMETHYL-2-AZABICYCLO[16.3.1]DOCOSA-4,6,10,18,21-PENTAENE-3,20,22-TRIONE, 9-CARBAMATE
GA
GELDANAMYCIN
GELDANAMYCIN, STREPTOMYCES HYGROSCOPICUS
nsc122750
GELDANAMYCIN (GDM)
GELDANAMYCIN FROM STREPTOMYCES*HYGROSCOP ICUS
GELDANAMYCIN, 99+%
Streptomyces hygroscopicus
2-Azabicyclo[16.3.1]docosa-4,6,10,18,21-pentaene-3,20,22-trione, 9,13-dihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-, 9-carbamate (8CI)
[(3R,5R,6S,7R,8E,10R,11R,12Z,14E)-6-Hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate
[(8Z,12Z,14Z)-6-hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate
9,13-Dihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-2-azabicyclo[16.3.1]docosa-4,6,10,18,21-pentaene-3,20,22-trione 9-Carbamate
NSC 212518
[(4Z,6E,8R,9R,10Z,12R,13R,14R,16R)-13-Hydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-4,6,10,18,21-pentaen-9-yl] carbamate
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-9-[(Aminocarbonyl)oxy]-13-hydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-2-azabicyclo[16.3.1]docosa-4,6,10,18,21(1)-pentene-3,20,22-trione
CP-122634 | [EINECS(EC#)]
999-999-2 | [Molecular Formula]
C29H40N2O9 | [MDL Number]
MFCD00274570 | [Molecular Weight]
560.64 | [MOL File]
30562-34-6.mol |
| Chemical Properties | Back Directory | [Appearance]
Yellow to Orange Powder | [Melting point ]
255 °C | [Boiling point ]
627.87°C (rough estimate) | [density ]
1.2443 (rough estimate) | [refractive index ]
1.5800 (estimate) | [Fp ]
87℃ | [storage temp. ]
−20°C
| [solubility ]
DMSO: soluble
| [form ]
powder
| [pka]
8.42±0.70(Predicted) | [color ]
yellow to orange
| [Usage]
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 ma | [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 Data | Back Directory | [Hazard Codes ]
T,Xi | [Risk Statements ]
R36/37/38:Irritating to eyes, respiratory system and skin . | [Safety Statements ]
S26:In case of contact with eyes, rinse immediately with plenty of water and seek medical advice .
S27:Take off immediately all contaminated clothing .
S36/37/39:Wear suitable protective clothing, gloves and eye/face protection . | [WGK Germany ]
2
| [RTECS ]
LX8920000
| [HS Code ]
29419090 |
| Hazard Information | Back Directory | [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.1,2,3 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.4 It also reduces signaling through mitogenic signaling proteins and interferes with steroid receptor function.1,5,6,7 Inhibitors of Hsp90, including geldanamycin, show promise in cancer therapy.8 | [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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