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Purity: ≥98%
Geldanamycin (U-29135; NSC-122750; NSC122750; U 29135) is a natural occurring, benzoquinone-based ,19-membered macrocyle ansamycin class of anticancer antibiotic. It is a crystalline antimicrobial and benzoquinone ansamycin compound extracted from the culture filtrates of Streptomyces hygroscopicus var. geldanus var. nova. Geldanamycin is a specific inhibitor of heat shock protein 90 (HSP90) with potential antineoplastic activity. It inhibits HSP90 with a Kd of 1.2 μM.
| Targets |
Hsp90 (Kd = 1.2 μM); anticancer antimicrobial/antibiotic
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| ln Vitro |
Viperin induction in RAW264.7 cells is considerably delayed and reduced by geldanamycin, suggesting a role for IRF3 in this process [1]. In cultured primary neurons, the benzoquinone ansamycin geldanamycin protects against neuronal damage caused by oxygen-glucose deprivation (OGD)/zVAD therapy. More significantly, Geldanamycin lowered RIP1 protein levels in a manner that was dependent on both time and concentration. Additionally, geldanamycin lowers Hsp90 protein levels, which causes RIP1 protein instability. As a result, RIP1 protein levels fall following geldanamycin treatment, although RIP1 mRNA levels remain unchanged [2]. The first known Hsp90 inhibitor found in a natural substance is geldanamycin. It inhibits the molecular chaperone function of Hsp90 by binding to its N-terminal ATPase domain, and through the apoptotic mechanism, it greatly causes tumor cell death [3].
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| ln Vivo |
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| Enzyme Assay |
Cortical neurons survival was evaluated by assaying lactate dehydrogenase (LDH) level in culture medium. After various treatments, the medium was collected and dropped on the VITROS Chemistry Products LDH DT slides to measured LDH level with an automatic biochemical-immune analyzer [2].
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| Cell Assay |
Western blot analysis [2]
Protein concentrations were determined by bicinchoninic acid protein assay after proteins were extracted from cells. Then equal amounts of protein (100 μg) were separated on 10% polyacrylamide gel electrophoresis and electrotransferred to nitrocellulose membrane. Blots were blocked with 5% non-fat dry milk and incubated with primary antibodies against RIP1, Hsp90, and β-actin at 4°C overnight. After washing, blots were incubated with secondary antibodies for 1 h. Blots were developed with odyssey system. Densitometric analysis of the bands was performed with the software Image J (V1.40). Immunoprecipitation[2] Harvested neuronal cells were lyzed and sonicated. Protein concentration was determined by a bicinchoninic acid protein method. Equal amounts of proteins were used for immuoprecipitation. The samples were incubated with protein A agarose beads for 2 h and then slightly centrifuged. The supernatants were incubated with RIP1 antibody at 4°C overnight with shaking. The second day, protein A agarose beads were added and rocked for 2 h at 4°C. After being centrifuged for 2 min at 10 000 g, beads were washed three times with lysis buffer. Finally, lysis buffer and 4× sample buffer were added to the beads and heated at 96°C for 5 min. The collected supernatants were subjected to western blot analysis. |
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| Additional Infomation |
Geldanamycin is 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. It has a role as an antiviral agent, an antineoplastic agent, an antimicrobial agent, a cysteine protease inhibitor and a Hsp90 inhibitor. It is an ansamycin, a carbamate ester, an organic heterobicyclic compound and a member of 1,4-benzoquinones.
Geldanamycin has been reported in Humicola fuscoatra and Streptomyces hygroscopicus with data available. Geldanamycin is a benzoquinone antineoplastic antibiotic isolated from the bacterium Streptomyces hygroscopicus. 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; the inhibition of HSP90 promotes the proteasomal degradation of oncogenic signaling proteins that may be over-expressed or overactive in tumor cells. (NCI04) |
| Molecular Formula |
C29H40N2O9
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| Molecular Weight |
560.64
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| Exact Mass |
560.273
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| Elemental Analysis |
C, 62.13; H, 7.19; N, 5.00; O, 25.68
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| CAS # |
30562-34-6
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| Related CAS # |
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| PubChem CID |
5288382
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| Appearance |
Light yellow to orange solid
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
783.9±60.0 °C at 760 mmHg
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| Melting Point |
255 °C
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| Flash Point |
427.9±32.9 °C
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| Vapour Pressure |
0.0±6.2 mmHg at 25°C
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| Index of Refraction |
1.559
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| LogP |
2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
40
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| Complexity |
1150
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| Defined Atom Stereocenter Count |
6
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| SMILES |
COC(C(C=C1NC(/C(C)=C/C=C/[C@H](OC)[C@@H](OC(N)=O)/C(C)=C/[C@H](C)[C@H]2O)=O)=O)=C(C[C@H](C[C@@H]2OC)C)C1=O
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| InChi Key |
QTQAWLPCGQOSGP-KSRBKZBZSA-N
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| InChi Code |
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
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| Chemical Name |
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-hydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.46 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (4.46 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7837 mL | 8.9184 mL | 17.8368 mL | |
| 5 mM | 0.3567 mL | 1.7837 mL | 3.5674 mL | |
| 10 mM | 0.1784 mL | 0.8918 mL | 1.7837 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00019708 | Terminated | Drug: tanespimycin | Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue |
National Cancer Institute (NCI) | June 1999 | Phase 1 |
| NCT00003969 | Completed | Drug: tanespimycin | Unspecified Adult Solid Tumor, Protocol Specific |
Cancer Research UK | August 1998 | Phase 1 |
| NCT01193491 | Terminated | Drug: IPI-493 | Hematologic Malignancies | Infinity Pharmaceuticals, Inc. | June 2010 | Phase 1 |
| NCT00093405 | Completed | Drug: tanespimycin | Kidney Cancer | Memorial Sloan Kettering Cancer Center |
August 2004 | Phase 2 |
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