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MedKoo Cat#: 202450 | Name: Retaspimycin HCl
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Retaspimycin, also known as IPI-504, is a potent and selective 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.

Chemical Structure

Retaspimycin HCl
Retaspimycin HCl
CAS#857402-63-2 (HCl)

Theoretical Analysis

MedKoo Cat#: 202450

Name: Retaspimycin HCl

CAS#: 857402-63-2 (HCl)

Chemical Formula: C31H46ClN3O8

Exact Mass:

Molecular Weight: 624.17

Elemental Analysis: C, 59.65; H, 7.43; Cl, 5.68; N, 6.73; O, 20.51

Price and Availability

Size Price Availability Quantity
10mg USD 650.00
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Related CAS #
857402-63-2 (HCl) 857402-23-4 (free base)
Synonym
IPI504; IPI-504; IPI504; Retaspimycin; Retaspimycin HCl; Retaspimycin hydrochloride
IUPAC/Chemical Name
[(3R,5S,6R,7S,8E,10S,11S,12Z,14E)-6,20,22-trihydroxy-5,11-dimethoxy-3,7,9,15-tetramethyl-16-oxo-21-(prop-2-enylamino)-17-azabicyclo[16.3.1]docosa-1(22),8,12,14,18,20-hexaen-10-yl] carbamate;hydrochloride
InChi Key
OIRUWDYJGMHDHJ-AFXVCOSJSA-N
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
SMILES Code
[H]Cl.NC(O[C@H]([C@@H](OC)/C=C\C=C(C)\C(N1)=O)/C(C)=C/[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(O)C1=CC(O)=C2NCC=C)=O
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
soluble in DMSO
Shelf Life
>5 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Phase I study of Retaspimycin: A phase 1 study of IPI-504 (retaspimycin hydrochloride) administered intravenously twice weekly for 2 weeks at 22.5, 45, 90, 150, 225, 300 or 400 mg/m(2) followed by 10 days off-treatment was conducted to determine the safety and maximum tolerated dose (MTD) of IPI-504 in patients with relapsed or relapsed/refractory multiple myeloma (MM). Anti-tumor activity and pharmacokinetics were also evaluated. Eighteen patients (mean age 60.5 years; median 9 prior therapies) were enrolled. No dose-limiting toxicities (DLTs) were reported for IPI-504 doses up to 400 mg/m(2). The most common treatment-related adverse event was grade 1 infusion site pain (four patients). All other treatment-related events were assessed as grade 1 or 2 in severity. The area under the curve (AUC) increased with increasing dose, and the mean half-life was approximately 2-4 h for IPI-504 and its metabolites. Four patients had stable disease, demonstrating modest single-agent activity in relapsed or relapsed/refractory MM.  (source: Leuk Lymphoma. 2011 Dec;52(12):2308-15.)    
Biological target:
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. Retaspimycin Hydrochloride is a potent inhibitor of Hsp90 with EC50s of 119 nM for both Hsp90 and Grp9.
In vitro activity:
In glioma cell lines, Hsp90 inhibition by IPI-504 induced apoptosis, blocked migration and invasion, and significantly decreased epidermal growth factor receptor levels, mitogen-activated protein kinase and/or Akt activities, and secretion of vascular endothelial growth factor. Reference: J Neurooncol. 2014 Dec;120(3):473-81. https://pubmed.ncbi.nlm.nih.gov/25115740/
In vivo activity:
Retaspimycin HCl at 300 mg/m² weekly in combination with trastuzumab was well tolerated and without significant toxicities in patients with advanced or metastatic HER2-positive breast cancer. The safety profile for patients in this study raises the possibility of retaspimycin HCl underdosing that limited efficacy. Reference: Breast Cancer Res Treat. 2013 May;139(1):107-13. https://pubmed.ncbi.nlm.nih.gov/23580070/
Solvent mg/mL mM
Solubility
DMSO 60.0 96.13
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 624.17 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Di K, Keir ST, Alexandru-Abrams D, Gong X, Nguyen H, Friedman HS, Bota DA. Profiling Hsp90 differential expression and the molecular effects of the Hsp90 inhibitor IPI-504 in high-grade glioma models. J Neurooncol. 2014 Dec;120(3):473-81. doi: 10.1007/s11060-014-1579-y. Epub 2014 Aug 13. PMID: 25115740. 2. Abramson JS, Chen W, Juszczynski P, Takahashi H, Neuberg D, Kutok JL, Takeyama K, Shipp MA. The heat shock protein 90 inhibitor IPI-504 induces apoptosis of AKT-dependent diffuse large B-cell lymphomas. Br J Haematol. 2009 Feb;144(3):358-66. doi: 10.1111/j.1365-2141.2008.07484.x. Epub 2008 Nov 13. PMID: 19036086; PMCID: PMC4029164. 3. Modi S, Saura C, Henderson C, Lin NU, Mahtani R, Goddard J, Rodenas E, Hudis C, O'Shaughnessy J, Baselga J. A multicenter trial evaluating retaspimycin HCL (IPI-504) plus trastuzumab in patients with advanced or metastatic HER2-positive breast cancer. Breast Cancer Res Treat. 2013 May;139(1):107-13. doi: 10.1007/s10549-013-2510-5. Epub 2013 Apr 12. PMID: 23580070; PMCID: PMC3646160. 4. Siegel D, Jagannath S, Vesole DH, Borello I, Mazumder A, Mitsiades C, Goddard J, Dunbar J, Normant E, Adams J, Grayzel D, Anderson KC, Richardson P. A phase 1 study of IPI-504 (retaspimycin hydrochloride) in patients with relapsed or relapsed and refractory multiple myeloma. Leuk Lymphoma. 2011 Dec;52(12):2308-15. doi: 10.3109/10428194.2011.600481. Epub 2011 Aug 18. PMID: 21851215.
In vitro protocol:
1. Di K, Keir ST, Alexandru-Abrams D, Gong X, Nguyen H, Friedman HS, Bota DA. Profiling Hsp90 differential expression and the molecular effects of the Hsp90 inhibitor IPI-504 in high-grade glioma models. J Neurooncol. 2014 Dec;120(3):473-81. doi: 10.1007/s11060-014-1579-y. Epub 2014 Aug 13. PMID: 25115740. 2. Abramson JS, Chen W, Juszczynski P, Takahashi H, Neuberg D, Kutok JL, Takeyama K, Shipp MA. The heat shock protein 90 inhibitor IPI-504 induces apoptosis of AKT-dependent diffuse large B-cell lymphomas. Br J Haematol. 2009 Feb;144(3):358-66. doi: 10.1111/j.1365-2141.2008.07484.x. Epub 2008 Nov 13. PMID: 19036086; PMCID: PMC4029164.
In vivo protocol:
1. Modi S, Saura C, Henderson C, Lin NU, Mahtani R, Goddard J, Rodenas E, Hudis C, O'Shaughnessy J, Baselga J. A multicenter trial evaluating retaspimycin HCL (IPI-504) plus trastuzumab in patients with advanced or metastatic HER2-positive breast cancer. Breast Cancer Res Treat. 2013 May;139(1):107-13. doi: 10.1007/s10549-013-2510-5. Epub 2013 Apr 12. PMID: 23580070; PMCID: PMC3646160. 2. Siegel D, Jagannath S, Vesole DH, Borello I, Mazumder A, Mitsiades C, Goddard J, Dunbar J, Normant E, Adams J, Grayzel D, Anderson KC, Richardson P. A phase 1 study of IPI-504 (retaspimycin hydrochloride) in patients with relapsed or relapsed and refractory multiple myeloma. Leuk Lymphoma. 2011 Dec;52(12):2308-15. doi: 10.3109/10428194.2011.600481. Epub 2011 Aug 18. PMID: 21851215.
1: Siegel D, Jagannath S, Vesole DH, Borello I, Mazumder A, Mitsiades C, Goddard J, Dunbar J, Normant E, Adams J, Grayzel D, Anderson KC, Richardson P. A phase 1 study of IPI-504 (retaspimycin hydrochloride) in patients with relapsed or relapsed and refractory multiple myeloma. Leuk Lymphoma. 2011 Dec;52(12):2308-15. Epub 2011 Aug 18. PubMed PMID: 21851215. 2: Floris G, Debiec-Rychter M, Wozniak A, Stefan C, Normant E, Faa G, Machiels K, Vanleeuw U, Sciot R, Schöffski P. The heat shock protein 90 inhibitor IPI-504 induces KIT degradation, tumor shrinkage, and cell proliferation arrest in xenograft models of gastrointestinal stromal tumors. Mol Cancer Ther. 2011 Oct;10(10):1897-908. Epub 2011 Aug 8. PubMed PMID: 21825009. 3: Oh WK, Galsky MD, Stadler WM, Srinivas S, Chu F, Bubley G, Goddard J, Dunbar J, Ross RW. Multicenter phase II trial of the heat shock protein 90 inhibitor, retaspimycin hydrochloride (IPI-504), in patients with castration-resistant prostate cancer. Urology. 2011 Sep;78(3):626-30. Epub 2011 Jul 18. PubMed PMID: 21762967; PubMed Central PMCID: PMC3166448. 4: Scaltriti M, Serra V, Normant E, Guzman M, Rodriguez O, Lim AR, Slocum KL, West KA, Rodriguez V, Prudkin L, Jimenez J, Aura C, Baselga J. Antitumor activity of the Hsp90 inhibitor IPI-504 in HER2-positive trastuzumab-resistant breast cancer. Mol Cancer Ther. 2011 May;10(5):817-24. Epub 2011 Mar 7. PubMed PMID: 21383049. 5: Normant E, Paez G, West KA, Lim AR, Slocum KL, Tunkey C, McDougall J, Wylie AA, Robison K, Caliri K, Palombella VJ, Fritz CC. The Hsp90 inhibitor IPI-504 rapidly lowers EML4-ALK levels and induces tumor regression in ALK-driven NSCLC models. Oncogene. 2011 Jun 2;30(22):2581-6. doi: 10.1038/onc.2010.625. Epub 2011 Jan 24. PubMed PMID: 21258415. 6: Roué G, Pérez-Galán P, Mozos A, López-Guerra M, Xargay-Torrent S, Rosich L, Saborit-Villarroya I, Normant E, Campo E, Colomer D. The Hsp90 inhibitor IPI-504 overcomes bortezomib resistance in mantle cell lymphoma in vitro and in vivo by down-regulation of the prosurvival ER chaperone BiP/Grp78. Blood. 2011 Jan 27;117(4):1270-9. Epub 2010 Nov 24. PubMed PMID: 21106982. 7: Sequist LV, Gettinger S, Senzer NN, Martins RG, Jänne PA, Lilenbaum R, Gray JE, Iafrate AJ, Katayama R, Hafeez N, Sweeney J, Walker JR, Fritz C, Ross RW, Grayzel D, Engelman JA, Borger DR, Paez G, Natale R. Activity of IPI-504, a novel heat-shock protein 90 inhibitor, in patients with molecularly defined non-small-cell lung cancer. J Clin Oncol. 2010 Nov 20;28(33):4953-60. Epub 2010 Oct 12. PubMed PMID: 20940188. 8: Douglas M, Lim AR, Porter JR, West K, Pink MM, Ge J, Wylie AA, Tibbits TT, Biggs K, Curtis M, Palombella VJ, Adams J, Fritz CC, Normant E. The antiproliferative activity of the heat shock protein 90 inhibitor IPI-504 is not dependent on NAD(P)H:quinone oxidoreductase 1 activity in vivo. Mol Cancer Ther. 2009 Dec;8(12):3369-78. Epub . PubMed PMID: 19952119. 9: Leow CC, Chesebrough J, Coffman KT, Fazenbaker CA, Gooya J, Weng D, Coats S, Jackson D, Jallal B, Chang Y. 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 Aug;8(8):2131-41. Epub 2009 Aug 11. PubMed PMID: 19671750. 10: Hanson BE, Vesole DH. Retaspimycin hydrochloride (IPI-504): a novel heat shock protein inhibitor as an anticancer agent. Expert Opin Investig Drugs. 2009 Sep;18(9):1375-83. Review. PubMed PMID: 19642950. 11: Abramson JS, Chen W, Juszczynski P, Takahashi H, Neuberg D, Kutok JL, Takeyama K, Shipp MA. The heat shock protein 90 inhibitor IPI-504 induces apoptosis of AKT-dependent diffuse large B-cell lymphomas. Br J Haematol. 2009 Feb;144(3):358-66. Epub 2008 Nov 13. PubMed PMID: 19036086. 12: Song D, Chaerkady R, Tan AC, García-García E, Nalli A, Suárez-Gauthier A, López-Ríos F, Zhang XF, Solomon A, Tong J, Read M, Fritz C, Jimeno A, Pandey A, Hidalgo M. Antitumor activity and molecular effects of the novel heat shock protein 90 inhibitor, IPI-504, in pancreatic cancer. Mol Cancer Ther. 2008 Oct;7(10):3275-84. PubMed PMID: 18852131. 13: Dewaele B, Wasag B, Cools J, Sciot R, Prenen H, Vandenberghe P, Wozniak A, Schöffski P, Marynen P, Debiec-Rychter M. Activity of dasatinib, a dual SRC/ABL kinase inhibitor, and IPI-504, a heat shock protein 90 inhibitor, against gastrointestinal stromal tumor-associated PDGFRAD842V mutation. Clin Cancer Res. 2008 Sep 15;14(18):5749-58. PubMed PMID: 18794084. 14: Patterson J, Palombella VJ, Fritz C, Normant E. 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. Epub 2007 Jul 12. PubMed PMID: 17624530. 15: Sydor JR, Normant E, Pien CS, Porter JR, Ge J, Grenier L, Pak RH, Ali JA, Dembski MS, Hudak J, Patterson J, Penders C, Pink M, Read MA, Sang J, Woodward C, Zhang Y, Grayzel DS, Wright J, Barrett JA, Palombella VJ, Adams J, Tong JK. 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. PubMed PMID: 17090671; PubMed Central PMCID: PMC1635022.

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