Retaspimycin Hydrochloride Chemical Properties

storage temp. 

Store at -20°C

solubility 

≥26.1 mg/mL in DMSO with gentle warming; insoluble in H2O; ≥100 mg/mL in EtOH with ultrasonic

form 

solid

color 

Off-white to pink

Retaspimycin Hydrochloride Usage And Synthesis

Uses

Retaspimycin Hydrochloride is a potent inhibitor of Hsp90 with EC50s of 119 nM for both Hsp90 and Grp9.

Definition

ChEBI: A hydrochloride that is the monohydrochloride salt of retaspimycin. A semi-synthetic water-soluble analogue of geldanamycin used in cancer treatment.

Biological Activity

retaspimycin hydrochloride (also known as ipi-504), a hydroquinone hydrochloride salt derivative of 17-aag, is a novel, potent and selective inhibitor of heat shock protein 90(hsp90) that binds to the amino-terminal atp/adp-binding site of hsp90. as a highly water-soluble version of 17-aag, ipi-504 (solubility > 200 mg/ml) does not need prior dissolution in organic solvents and hence can be delivered in high concentrations. once in the systemic circulation, ipi-504 is deprotonated and converted into the free base ipi-504 which is subsequently oxidized to 17-aag. ipi-504 potently inhibits proliferation in several tumor cell lines with 50% inhibition concentration ic50 values ranging from 10-40 nmol/l and has been used for the treatment of gastrointestinal stromal tumors, soft-tissue sarcomas and non-small cell lung cancer.britt erika hanson and david h vesole. retaspimycin hydrochloride (ipi-504): a novel heat shock protein inhibitor as an anticancer agent. expert opin. investi. drugs (2009) 18(9): 1375-1383david siegel, sundar jagannath, david h. vesole, ivan borello, amitabha mazumder, constantine mitsiades, jill goddard, joi dunbar, emmanuel normant, julian adams, david grayzel, kenneth c. anderson and paul richardson. a phase 1 study of ipi-504 (retaspimycin hydrochloride) in patients with relapsed or relapsed and refractory multiple myeloma. leukemia & lymphoma, 2011; 52(12): 2308-2315ching ching leow, jon chesebrough, karen t. coffman, christine a. fazenbaker, john gooya, david weng, steve coats, dowdy jackson, bahija jallal and yong chang. antitumor efficacy of ipi-504, a selective heat shock protein 90 inhibitor against human epidermal growth factor receptor 2-positive human xenograft models as a single agent and in combination with trastuzumab or lapatinib. mol cancer ther 2009; 8: 2131-2141

in vivo

target

HSP90

IC 50

HSP90: 119 nM (EC₅₀); GRP94: 119 nM (EC₅₀)

References

[1] Patterson J, et al. IPI-504, a novel and soluble HSP-90 inhibitor, blocks the unfolded protein response in multiple myeloma cells. Cancer Chemother Pharmacol. 2008 May;61(6):923-32. DOI:10.1007/s00280-007-0546-0
[2] Scaltriti M, et al. Antitumor Activity of the Hsp90 Inhibitor IPI-504 in HER2-Positive Trastuzumab-Resistant Breast Cancer. Mol Cancer Ther. 2011 May;10(5):817-24. DOI:10.1158/1535-7163.MCT-10-0966
[3] Sydor JR, et al. Development of 17-allylamino-17-demethoxygeldanamycin hydroquinone hydrochloride (IPI-504), an anti-cancer agent directed against Hsp90. Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17408-13. Epub 2006 Nov 7. DOI:10.1073/pnas.0608372103

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