Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C29H40N2O9 |
| Molecular Weight | 560.6359 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 6 / 6 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CO[C@H]1C[C@H](C)CC2=C(OC)C(=O)C=C(NC(=O)\C(C)=C\C=C[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@H]1O)C2=O
InChI
InChIKey=QTQAWLPCGQOSGP-KSRBKZBZSA-N
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
| Molecular Formula | C29H40N2O9 |
| Molecular Weight | 560.6359 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 6 / 6 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Geldanamycin, an antimicrobial compound, was purified in 1970 from the culture filtrates of Streptomyces hygroscopicus var. geldanus var. nova. Geldanamycin is moderately active in vitro against protozoa, bacteria, and fungi. It also has an antineoplastic effect against some cancer cells growing in culture. Molecular studies revealed the binding of geldanamycin to members of the heat shock protein 90 (HSP90) family of molecular chaperones. Interference with the function of these HSPs seems to be the major mechanism of action of geldanamycin.
CNS Activity
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. | 1995 |
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| 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-mediated membrane translocation of c-Src protein kinase in liver WB-F344 cells. | 1999 Apr-May |
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| The benzoquinone ansamycin geldanamycin stimulates proteolytic degradation of focal adhesion kinase. | 1999 Jan |
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| Geldanamycin induces heat shock protein expression through activation of HSF1 in K562 erythroleukemic cells. | 1999 Oct |
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| Destabilization of steroid receptors by heat shock protein 90-binding drugs: a ligand-independent approach to hormonal therapy of breast cancer. | 2001 Jul |
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| HSP90 inhibitors alter capsaicin- and ATP-induced currents in rat dorsal root ganglion neurons. | 2002 Mar 25 |
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| Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via the proteosome pathway in prostate cancer cells. | 2002 May 1 |
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| Ligand-dependent and independent modulation of aryl hydrocarbon receptor localization, degradation, and gene regulation. | 2002 Oct |
|
| ATPase inhibitors suppress actinomycin D-induced apoptosis in leukemia cells. | 2002 Sep-Oct |
|
| PI3K/Akt is required for heat shock proteins to protect hypoxia-inducible factor 1alpha from pVHL-independent degradation. | 2004 Apr 2 |
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| Hair growth induction by the Tellurium immunomodulator AS101: association with delayed terminal differentiation of follicular keratinocytes and ras-dependent up-regulation of KGF expression. | 2004 Feb |
|
| Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells' sensitivity to cytotoxic drugs. | 2004 Mar 1 |
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| Apoptosis induction by a novel retinoid-related molecule requires nuclear factor-kappaB activation. | 2005 Jun 1 |
|
| 15-Hydroxyprostaglandin dehydrogenase can be induced by dexamethasone and other glucocorticoids at the therapeutic level in A549 human lung adenocarcinoma cells. | 2005 Mar 1 |
|
| Increased expression of the MGMT repair protein mediated by cysteine prodrugs and chemopreventative natural products in human lymphocytes and tumor cell lines. | 2007 Feb |
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| Resistance to geldanamycin-induced apoptosis in differentiated neuroblastoma SH-SY5Y cells. | 2007 Mar 6 |
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| Aryl hydrocarbon receptor signaling in rainbow trout hepatocytes: role of hsp90 and the proteasome. | 2007 Nov |
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| Geldanamycin induces production of heat shock protein 70 and partially attenuates ototoxicity caused by gentamicin in the organ of Corti explants. | 2009 Sep 2 |
|
| The inhibitory mechanisms of the tyrosine kinase inhibitors herbimycin a, genistein, and tyrphostin B48 with regard to the function of the aryl hydrocarbon receptor in Caco-2 cells. | 2010 |
|
| Solanesol protects human hepatic L02 cells from ethanol-induced oxidative injury via upregulation of HO-1 and Hsp70. | 2015 Apr |
|
| The quinone methide aurin is a heat shock response inducer that causes proteotoxic stress and Noxa-dependent apoptosis in malignant melanoma cells. | 2015 Jan 16 |
Patents
Sample Use Guides
In Vivo Use Guide
Curator's Comment: Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent.
Maximum tolerated doses were approximately 20 mg/kg for the mice and 4 mg/kg for the dog.
Route of Administration:
Intravenous
The mechanism of action of geldanamycin was investigated with murine lymphoblastoma L5178Y cells. The agent inhibited the cell growth at concentrations over 0.01 micrograms/ml. Geldanamycin blocked DNA polymerase alpha more markedly than beta and gamma. The degree of inhibition depended upon concentrations of the enzyme but not upon those of template, suggesting a drug-enzyme interaction. IC50 for DNA polymerase alpha was 10 micrograms/ml and for DNA polymerase beta 100 micrograms/ml at low concentrations of enzyme. The inhibition of DNA polymerase alpha by the antibiotic was non-competitive and Ki was 20 microM.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 19:22:15 GMT 2023
by
admin
on
Fri Dec 15 19:22:15 GMT 2023
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| Record UNII |
Z3K3VJ16KU
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| Record Status |
Validated (UNII)
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| Record Version |
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C1003
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m5686
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| Related Record | Type | Details | ||
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT |
