| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Tanespimycin (formerly NSC-330507; CP-127374; 17-AAG, BAY-579352, KOS-953, 17-AAG, CP-127374), a benzoquinone analog and a derivative of the antibiotic geldanamycin, is an orally bioavailable and small-molecule inhibitor of heat shock protein 90/HSP90 with potential antitumor activity. It inhibits HSP90 with an IC50 of 5 nM in a cell-free assay. Tanespimycin is being studied for the treatment of cancer, specifically in younger patients with certain types of leukemia or solid tumors, especially kidney tumors.
| Targets |
HSP90 (IC50 = 5 nM); Mitophagy; Autophagy
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| ln Vitro |
Tanespimycin degrades HER2, Akt, and the G1 growth halt of prostate cancer cells that is dependent on retinoblastoma as well as mutant and wild-type AR. With IC50 values ranging from 25 to 45 nM (LNCaP, 25 nM; LAPC-4, 40 nM; DU-145, 45 nM; and PC-3, 25 nM), tantespimycin suppresses prostate cancer cell lines [1]. Tanespimycin (0.1–1 μM) causes breast cancer cells that overexpress ErbB2 to almost completely lose ErbB2[2]. Tanespimycin downregulates Bcl-2, Survivin, and Cyclin B1, and upregulates cleaved PARP. These effects prevent the development of CCA cells and cause G2/M cell cycle arrest and apoptosis[3].
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| ln Vivo |
In prostate cancer xenografts, tantespimycin (25–200 mg/kg, ip) reduces AR, HER2, and Akt expression in a dose-dependent manner. At doses high enough to cause the degradation of HER2, Akt, and AR, tantespimycin dose-dependently suppresses the growth of androgen-dependent and -independent prostate cancer xenografts without causing toxicity [1]. Through tail vein injection, tanespimycin (60 mg/kg) and Rapamycin (30 mg/kg) impacted tumor cure in MDA-MB-231 tumor-bearing rats by inhibiting the growth of A549 and MDA-MB-231 tumors [4].
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| Enzyme Assay |
Heat shock protein 90 (Hsp90) is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signalling proteins, including HER-2/ErbB2, Akt, Raf-1, Bcr-Abl and mutated p53. Hsp90 inhibitors bind to Hsp90, and induce the proteasomal degradation of Hsp90 client proteins. Although Hsp90 is highly expressed in most cells, Hsp90 inhibitors selectively kill cancer cells compared to normal cells, and the Hsp90 inhibitor 17-allylaminogeldanamycin (17-AAG) is currently in phase I clinical trials. However, the molecular basis of the tumour selectivity of Hsp90 inhibitors is unknown. Here we report that Hsp90 derived from tumour cells has a 100-fold higher binding affinity for 17-AAG than does Hsp90 from normal cells. Tumour Hsp90 is present entirely in multi-chaperone complexes with high ATPase activity, whereas Hsp90 from normal tissues is in a latent, uncomplexed state. In vitro reconstitution of chaperone complexes with Hsp90 resulted in increased binding affinity to 17-AAG, and increased ATPase activity. These results suggest that tumour cells contain Hsp90 complexes in an activated, high-affinity conformation that facilitates malignant progression, and that may represent a unique target for cancer therapeutics[5].
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| Cell Assay |
The aim of this study was to investigate the effects of 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a heat shock protein 90 (HSP90) inhibitor, on the proliferation, cell cycle, and apoptosis of human cholangiocarcinoma (CCA) cells. Cell proliferation and cell cycle distribution were measured by the MTT assay and flow cytometry analysis, respectively. Induction of apoptosis was determined by flow cytometry and Hoechst staining. The expressions of cleaved poly ADP-ribose polymerase (PARP), Bcl-2, Survivin, and Cyclin B1 were detected by Western blot analysis. The activity of caspase-3 was also examined. We found that 17-AAG inhibited cell growth and induced G2/M cell cycle arrest and apoptosis in CCA cells together with the down-regulation of Bcl-2, Survivin and Cyclin B1, and the up-regulation of cleaved PARP. Moreover, increased caspase-3 activity was also observed in CCA cells treated with 17-AAG. In conclusion, our data suggest that the inhibition of HSP90 function by 17-AAG may provide a promising therapeutic strategy for the treatment of human CCA[3].
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| Additional Infomation |
Tanespimycin is a 19-membered macrocyle that is geldanamycin in which the methoxy substituent attached to the benzoquinone moiety has been replaced by an allylamino group. It is a potent inhibitor of heat shock protein 90 (Hsp90). A less toxic analogue than geldanamycin, it induces apoptosis and displays antitumour effects. It has a role as an antineoplastic agent, a Hsp90 inhibitor and an apoptosis inducer. It is a secondary amino compound, an ansamycin, a carbamate ester, an organic heterobicyclic compound and a member of 1,4-benzoquinones. It is functionally related to a geldanamycin.
Tanespimycin, manufactured by Conforma Therapeutics is under development as a small molecule inhibitor of heat shock protein 90 (HSP90). It is developed for the treatment of several types of cancer, solid tumors or chronic myelogenous leukemia. Tanespimycin is a benzoquinone antineoplastic antibiotic derived from the antineoplastic antibiotic geldanamycin. Tanespimycin 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 overexpressed by tumor cells. Drug Indication Investigated for use/treatment in leukemia (myeloid) and solid tumors. Mechanism of Action Tanespimycin is a small molecule inhibitor of heat shock protein 90 (HSP90). HSP90 is a molecular “chaperone” protein that controls protein shape or conformation, including that of key signaling molecules involved in the growth and survival of tumor cells. |
| Molecular Formula |
C31H43N3O8
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| Molecular Weight |
585.69
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| Exact Mass |
585.304
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| Elemental Analysis |
C, 63.57; H, 7.40; N, 7.17; O, 21.85
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| CAS # |
75747-14-7
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| Related CAS # |
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| PubChem CID |
6505803
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| Appearance |
Purple to purplish red solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
797.8±60.0 °C at 760 mmHg
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| Melting Point |
201-203ºC
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| Flash Point |
436.3±32.9 °C
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| Vapour Pressure |
0.0±6.4 mmHg at 25°C
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| Index of Refraction |
1.566
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| LogP |
2.68
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
42
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| Complexity |
1210
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| Defined Atom Stereocenter Count |
6
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| SMILES |
C[C@H]1C[C@@H]([C@@H]([C@H](/C=C(/[C@@H]([C@H](/C=C\C=C(\C(=O)NC2=CC(=O)C(=C(C1)C2=O)NCC=C)/C)OC)OC(=O)N)\C)C)O)OC
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| InChi Key |
AYUNIORJHRXIBJ-HTLBVUBBSA-N
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| InChi Code |
InChI=1S/C31H43N3O8/c1-8-12-33-26-21-13-17(2)14-25(41-7)27(36)19(4)15-20(5)29(42-31(32)39)24(40-6)11-9-10-18(3)30(38)34-22(28(21)37)16-23(26)35/h8-11,15-17,19,24-25,27,29,33,36H,1,12-14H2,2-7H3,(H2,32,39)(H,34,38)/b11-9+,18-10+,20-15+/t17-,19+,24+,25+,27-,29+/m1/s1
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| Chemical Name |
(4E,6E,8S,9S,10E,12S,13R,14S,16R)-19-(allylamino)-13-hydroxy-8,14-dimethoxy-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 |
NSC330507; CP127374; 17-AAG, BAY 579352, KOS-953, 17 AAG, CP-127374, NSC-330507, NSC 330507; CP 127374; 17AAG, BAY 57-9352, BAY579352, KOS 953, KOS953, Tanespimycin; 75747-14-7; 17-AAG; 17-(Allylamino)-17-demethoxygeldanamycin; 17AAG; NSC-330507; 17-(Allylamino)geldanamycin
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
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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: ≥ 5 mg/mL (8.54 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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. Solubility in Formulation 2: ≥ 5 mg/mL (8.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 5 mg/mL (8.54 mM) in 15% Cremophor EL + 85% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: ≥ 1.62 mg/mL (2.77 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.2 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 5: 5%DMSO+corn oil: 10 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7074 mL | 8.5369 mL | 17.0739 mL | |
| 5 mM | 0.3415 mL | 1.7074 mL | 3.4148 mL | |
| 10 mM | 0.1707 mL | 0.8537 mL | 1.7074 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 |
| NCT00118248 | Completed Has Results | Drug: tanespimycin | Recurrent Thyroid Cancer Stage IV Follicular Thyroid Cancer |
National Cancer Institute (NCI) | December 2004 | Phase 2 |
| NCT00564928 | Completed | Drug: IPI-504 | Prostate Cancer Prostatic Neoplasms |
Infinity Pharmaceuticals, Inc. | November 2007 | Phase 2 |
| NCT00098423 | Completed | Drug: tanespimycin Drug: cytarabine |
Accelerated Phase Chronic Myelogenous Leukemia |
National Cancer Institute (NCI) | November 2004 | Phase 1 |
| NCT00093821 | Completed | Drug: tanespimycin | Childhood Chronic Myelogenous Leukemia |
National Cancer Institute (NCI) | September 2004 | Phase 1 |
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