| Size | Price | |
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| 500mg | ||
| 1g | ||
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Retaspimycin (IPI504; IPI-504) is a novel and potent inhibitor of Hsp90 with anticancer activity. It exhibits EC50s of 119 nM for both Hsp90 and Grp9.
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| ln Vitro |
Retaspimycin has EC50s of 119 nM for both Grp9 and Hsp90, making it a strong inhibitor of Hsp90. Human multiple myeloma (MM) cell lines are cytocoxic to reticopiracil (IPI-504); the EC50s for MM1.s and RPMI-8226 cells are 307 ± 51 nM and 306 ± 38 nM, respectively[1]. In a dose-dependent way, retispimycin (IPI-504, 10-100 nM) inhibits the proliferation of cells that are both trastuzumab-sensitive and -resistant. In both susceptible and trastuzumab-resistant cells, retispimycin (0–500 nM) suppresses the Akt and MAPK pathways and lowers the expression of the HER2 protein[3].
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| ln Vivo |
In tumor-bearing RPMI-8226 mice, retispimycin (IPI-504, 50 mg/kg, iv) selectively retains tumors[1]. In GIST-882 and GIST-PSW xenografts, retaspimycin (IPI-504, 100 mg/kg, po, 3 times per week) decreases the tumor volume by 69% and 84% of baseline values, respectively. Additionally, in the GIST-PSW model, retaspimycin plus imatinib slows tumor growth more than retaspimycin alone does, but in the GIST-882 model, there is no discernible difference. In gastrointestinal stromal tumors (GISTs), retaspimycin also downregulates KIT[2]. In HCC1569 xenografts, retispimycin (IPI-504, 50 mg/kg) exhibits anticancer efficacy. In BT474R and BT474H1047R tumors, IPI-504 (100 mg/kg, ip) efficiently reduces the levels of HER2, p-Akt, and p-MAPKs[3].
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| Additional Infomation |
Retaspimycin is an ansamycin that is tanespimycin in which the benzoquinone moiety has been reduced to the corresponding hydroquinone. A semi-synthetic analogue of geldanamycin, it is used (generally as the hydrochloride salt) in cancer treatment. It has a role as a Hsp90 inhibitor and an antineoplastic agent. It is a member of hydroquinones, an ansamycin, an organic heterobicyclic compound, a secondary amino compound, a semisynthetic derivative and a carbamate ester. It is functionally related to a geldanamycin. It is a conjugate base of a retaspimycin(1+).
Retaspimycin is a small-molecule inhibitor of heat shock protein 90 (HSP90) with antiproliferative and antineoplastic activities. Retaspimycin binds to and inhibits the cytosolic chaperone functions of HSP90, which maintains the stability and functional shape of many oncogenic signaling proteins and may be overexpressed or overactive in tumor cells. Retaspimycin-mediated inhibition of HSP90 promotes the proteasomal degradation of oncogenic signaling proteins in susceptible tumor cell populations, which may result in the induction of apoptosis. See also: Retaspimycin Hydrochloride (annotation moved to). Drug Indication Investigated for use/treatment in gastric cancer, lung cancer, and multiple myeloma. |
| Molecular Formula |
C31H45N3O8
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|---|---|
| Molecular Weight |
587.704309225082
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| Exact Mass |
587.32
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| CAS # |
857402-23-4
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| Related CAS # |
Retaspimycin Hydrochloride;857402-63-2
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| PubChem CID |
11534420
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
800.9±65.0 °C at 760 mmHg
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| Flash Point |
438.2±34.3 °C
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| Vapour Pressure |
0.0±3.0 mmHg at 25°C
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| Index of Refraction |
1.587
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| LogP |
2.62
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| Hydrogen Bond Donor Count |
6
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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 |
999
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| Defined Atom Stereocenter Count |
6
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| SMILES |
O(C)[C@@H]1C([C@@H](C)C=C(C)[C@@H]([C@H](C=CC=C(C)C(NC2C=C(C(=C(C=2O)C[C@H](C)C1)NCC=C)O)=O)OC)OC(N)=O)O |c:6,11,t:13|
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| InChi Key |
OAKGNIRUXAZDQF-TXHRRWQRSA-N
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| InChi Code |
InChI=1S/C31H45N3O8/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/h8-11,15-17,19,24-25,27,29,33,35-37H,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,6Z,8S,9S,10E,12S,13R,14S,16R)-13,20,22-trihydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3-oxo-19-(prop-2-enylamino)-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18(22),19-hexaen-9-yl] carbamate
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7015 mL | 8.5077 mL | 17.0155 mL | |
| 5 mM | 0.3403 mL | 1.7015 mL | 3.4031 mL | |
| 10 mM | 0.1702 mL | 0.8508 mL | 1.7015 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.
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