1. Cell Cycle/DNA Damage
    Metabolic Enzyme/Protease
  2. HSP

Retaspimycin Hydrochloride (Synonyms: IPI-504)

Cat. No.: HY-10210 Purity: >95.0%
Handling Instructions

Retaspimycin hydrochloride is a novel and highly soluble inhibitor of the Hsp90 ATPase activity, with EC50s of 119 nM for both Hsp90 and Grp9.

For research use only. We do not sell to patients.

Retaspimycin Hydrochloride Chemical Structure

Retaspimycin Hydrochloride Chemical Structure

CAS No. : 857402-63-2

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 297 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
1 mg USD 108 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
5 mg USD 216 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
10 mg USD 330 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
50 mg USD 900 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
100 mg USD 1512 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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Other Forms of Retaspimycin Hydrochloride:

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Retaspimycin hydrochloride is a novel and highly soluble inhibitor of the Hsp90 ATPase activity, with EC50s of 119 nM for both Hsp90 and Grp9.

IC50 & Target[3]

HSP90

119 nM (EC50)

GRP94

119 nM (EC50)

In Vitro

Retaspimycin (IPI-504) is a novel and highly soluble analog of 17AAG, an inhibitor of Hsp90. Retaspimycin can abrogate both the unfolded protein response element (UPRE) and ERSE-driven luciferase activity in non-treated U266 and MM.1s cells as well as in Tunicamycin (Tm)-treated cells. The IC50s for the inhibition of reporter gene activity by Retaspimycin are 196±56 nM in U266 and 472±177 nM in MM.1s for UPRE-luc activity and 213±140 nM for the ERSE-driven activity in MM.1s cells. Retaspimycin treatment leads to a dose-dependent decrease of p50ATF6 with EC50 of 237 nM, consistent with the reporter-gene assay. The level of sXBP1 is decreased in the presence of Retaspimycin with an apparent EC50 between 300 nM and 1 μM[1]. Incubation of Retaspimycin (IPI-504) potently suppresses both Akt and MAPKs phosphorylation in both sensitive and Trastuzumab-resistant cells. Total levels of Akt decreased in all 4 cell lines (BT474, SKBR-3, HCC1569, and HCC1569) in a dose-dependent manner. However, levels of total MAPKs are not significantly altered with Retaspimycin treatment[2].

In Vivo

Retaspimycin (IPI-504) and Trastuzumab independently induce tumor regression of Trastuzumab-sensitive BT474 cell-derived xenografts. Xenografts derived from BT474R cells continue to grow in the presence of Trastuzumab but are still sensitive to Retaspimycin. When used in combination, Retaspimycin and Trastuzumab add only marginal benefits to Retaspimycin monotherapy. Retaspimycin (100 mg/kg) as a single agent is more efficacious than Trastuzumab in inhibiting tumor growth in HCC1569 xenografts. The combination is not significantly superior to Retaspimycin used as a single agent[2].

Clinical Trial
References
Preparing Stock Solutions
Concentration Volume Mass 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
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[1]

Retaspimycin (IPI-504) is solubilized in DMSO and stored, and then diluted with appropriate media before use[1].

Hela cells are grown in Dulbecco’s modified Eagle’s medium containing 10% fetal bovine serum, 1 ug/mL streptomycin and 1 ug/mL penicillin. U266 and MM.1s are cultured in RPMI 1640 medium containing 15% fetal bovine serum, 1 mM pyruvate, 1 ug/mL streptomycin, and 1 ug/mL penicillin. All the cell lines are maintained at 37°C in a humidified 5% CO2 atmosphere. Viability studies are performed using the vital mitochondrial function stain Alamar Blue. After cells are incubated in 96-well plates (200 μL) ± Retaspimycin, 20 μL of Alamar Blue is added and incubated for 4-6 h at 37°C. The Alamar Blue reduction is monitored using an Envision plate reader at λEM=544 nm and λEM=590 nm. The ratios obtained from drug-treated cells versus vehicle treated cells are quantified and plotted against drug concentration to give EC50 values. Caspase-3 and 7 activities are detected using the Caspase Glow kit[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

Retaspimycin (IPI-504) is prepared in sterile PBS (Mice)[2].

Mice[2]
For all the experiments, 2×107 cells are injected into the right flanks of 10 mice for each experimental condition. Established tumors are treated with Trastuzumab, Retaspimycin, or the combination as following: Trastuzumab (10 mg/kg in sterile PBS) or sterile PBS (control) is given intraperitoneally twice weekly. Retaspimyci (100 mg/kg) is administered intraperitoneally thrice weekly. Retaspimyci, Trastuzumab, and the combination treatments are tolerable. No significant toxicity is noticed among the treatment arms. Tumor growth is measured with digital calipers as indicated and tumor volume is determined using the formula: (length×width2)×(π/6). At the end of the experiments, the animals are anesthetized with 1.5% isofluorane-air mixture and killed by cervical dislocation. Results are depicted as means of tumor volume±SE. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

624.17

Formula

C₃₁H₄₆ClN₃O₈

CAS No.

857402-63-2

SMILES

O=C(NC1=C2O)/C(C)=C/C=C\[[email protected]](OC)[[email protected]](/C(C)=C/[[email protected]@H]([[email protected]]([[email protected]](C[[email protected]@H](CC2=C(C(O)=C1)NCC=C)C)OC)O)C)OC(N)=O.Cl

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 56 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: >95.0%

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Product Name:
Retaspimycin Hydrochloride
Cat. No.:
HY-10210
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