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| ln Vitro |
Retaspimycin (IPI-504) is a Hsp90 inhibitor and a new, highly soluble derivative of 17AAG. In both tunicamycin (Tm)-treated and untreated U266 and MM.1s cells, retispimycin eliminates ERSE-driven luciferase activity and unfolded protein response element (UPRE). The IC50 of retaspimycin was found to be 196±56 nM in U266; 472±177 nM in MM.1s for UPRE-luc activity; and 213±140 nM in MM.1s cells for ERSE-driver activity. In line with the reporter gene experiment, retispimycin administration caused a dose-dependent drop in p50ATF6 with an EC50 of 237 nM. Retaspimycin causes sXBP1 levels to drop, with an apparent EC50 ranging from 300 nM to 1 μM [1]. Both trastuzumab-resistant and sensitive cells' Akt and MAPK phosphorylation are efficiently inhibited by retaspimycin (IPI-504) incubation. In all four cell lines (BT474, SKBR-3, HCC1569, and HCC1569), total Akt levels dropped in a dose-dependent way. Nonetheless, following retaspimycin treatment, overall MAPK levels did not significantly alter [2].
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| ln Vivo |
In xenografts produced from trastuzumab-sensitive BT474 cells, retispimycin (IPI-504) and trastuzumab separately cause tumor regression. Transtuzumab did not stop the growth of xenografts made from BT474R cells, but they did not lose their sensitivity to retispimycin hydrochloride. Retaspimycin monotherapy gains minimal additional benefit from the combination of retaspimycin and trastuzumab. In HCC1569 xenografts, retaspimycin (100 mg/kg) was found to be a more potent single drug in suppressing tumor development than trastuzumab. Retaspimycin taken alone was not appreciably superior than the combination [2].
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| Additional Infomation |
Retaspimycin hydrochloride is a hydrochloride that is the monohydrochloride salt of retaspimycin. A semi-synthetic water-soluble analogue of geldanamycin used in cancer treatment. It has a role as a Hsp90 inhibitor and an antineoplastic agent. It contains a retaspimycin(1+).
Retaspimycin Hydrochloride is the hydrochloride salt of 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. |
| Molecular Formula |
C31H45N3O8.HCL
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|---|---|
| Molecular Weight |
624.16524
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| Exact Mass |
623.297
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| CAS # |
857402-63-2
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| Related CAS # |
Retaspimycin;857402-23-4
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| PubChem CID |
11685945
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| Appearance |
Off-white to pink solid powder
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| LogP |
6.093
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| Hydrogen Bond Donor Count |
7
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
43
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| Complexity |
999
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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(=C(C(=C2O)C1)NCC=C)O)/C)OC)OC(=O)N)\C)C)O)OC.Cl
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| InChi Key |
OIRUWDYJGMHDHJ-AFXVCOSJSA-N
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| InChi Code |
InChI=1S/C31H45N3O8.ClH/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);1H/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;hydrochloride
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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: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
1M HCl : 100 mg/mL (~160.21 mM)
DMSO : ~60 mg/mL (~96.13 mM) H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (4.81 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 30.0 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: 3 mg/mL (4.81 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 30.0 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 | 1.6021 mL | 8.0106 mL | 16.0213 mL | |
| 5 mM | 0.3204 mL | 1.6021 mL | 3.2043 mL | |
| 10 mM | 0.1602 mL | 0.8011 mL | 1.6021 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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