Ganetespib (STA-9090)

For research use only.

Catalog No.S1159

44 publications

Ganetespib (STA-9090) Chemical Structure

CAS No. 888216-25-9

Ganetespib (STA-9090) is an HSP90 inhibitor with IC50 of 4 nM in OSA 8 cells, induces apoptosis of OSA cells while normal osteoblasts are not affected; active metabolite of STA-1474. Phase 3.

Selleck's Ganetespib (STA-9090) has been cited by 44 publications

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Choose Selective HSP (HSP90) Inhibitors

Biological Activity

Description Ganetespib (STA-9090) is an HSP90 inhibitor with IC50 of 4 nM in OSA 8 cells, induces apoptosis of OSA cells while normal osteoblasts are not affected; active metabolite of STA-1474. Phase 3.
Targets
HSP90 [1]
(OSA 8 cells)
4 nM
In vitro

The 50% inhibitory concentrations (IC50) for Ganetespib against malignant mast cell lines are 10-50 times lower than that for 17-AAG, indicating that triazolone class of HSP90 inhibitors likely exhibits greater potency than geldanamycin based inhibitors. [1] Ganetespib inhibits MG63 cell lines with IC50 of 43 nM. [1] Ganetespib binds to the ATP-binding domain at the N-terminus of Hsp90 and serves as a potent Hsp90 inhibitor by causing degradation of multiple oncogenic Hsp90 client proteins including HER2/neu, mutated EGFR, Akt, c-Kit, IGF-1R, PDGFRα, Jak1, Jak2, STAT3, STAT5, HIF-1α, CDC2 and c-Met as well as Wilms' tumor 1. [2] Ganetespib, at low nanomolar concentrations, potently arrests cell proliferation and induces apoptosis in a wide variety of human cancer cell lines, including many receptor tyrosine kinase inhibitor- and tanespimycin-resistant cell lines. Ganetespib exhibits potent cytotoxicity in a range of solid and hematologic tumor cell lines, including those that express mutated kinases that confer resistance to small-molecule tyrosine kinase inhibitors. [3] Ganetespib treatment rapidly caused the degradation of known Hsp90 client proteins, exhibits superior potency to the ansamycin inhibitor 17-AAG, and shows sustained activity even with short exposure times.[3] In anohter study, Ganetespib induces apoptosis of malignant canine mast cell lines. Ganetespib is active at significantly lower concentrations for C2 and BR canine malignant mast cells with IC50 of 19 and 4 nM, respectively, while 17-AAG inhibits C2 and BR canine malignant mast cells with IC50 of 958 and 44 nM, respectively. [4] Both the expression of WT and mutant Kit are downregulated by 100 nM Ganetespib after 24 hours in all lines treated including C2 and BMCMCs cells. However, no effects on PI3K or HSP90 expression are observed following treatment with Ganetespib.[4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NCI-H1975 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn\PO|IhcA>? NYriXoh4UUN3ME24JI5O MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF2NE[2OUc,OjJzNES2OlU9N2F-
NCI-H1975 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3rJeFQ5KGh? NXG4SoFOUUN3ME2xOkBvVQ>? M{ThTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MUS0OlY2Lz5{MkG0OFY3PTxxYU6=
Calu-6 NW\WcYdbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NInscoVKSzVyPU[0JI5O NITSWYk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{CxNlI1QCd-MkOwNVIzPDh:L3G+
Calu-1 NXHMcHVrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYTJR|UxRTV6IH7N M37h[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MEGyNlQ5Lz5{M{CxNlI1QDxxYU6=
H2122 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWrJR|UxRTV|IH7N M1PDR|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MEGyNlQ5Lz5{M{CxNlI1QDxxYU6=
A549 M4D1cGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUfTSYhlUUN3ME20N{BvVQ>? MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzBzMkK0PEc,OjNyMUKyOFg9N2F-
H358 NIfIOmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYLJR|UxRTJ7IH7N M2jJT|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MEGyNlQ5Lz5{M{CxNlI1QDxxYU6=
H1734 M1jQd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF\4S5pKSzVyPUK4JI5O MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzBzMkK0PEc,OjNyMUKyOFg9N2F-
H727 NF\RPGJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{nwb2lEPTB;Mkigcm0> MnPZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjNyMUKyOFgoRjJ|MEGyNlQ5RC:jPh?=
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LAN-5 MXfxTHRUKGG|c3H5 MVPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVEGQLUWgZ4VtdHN? Mn;WQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
Rh18 MlvZdWhVWyCjc4PhfS=> NWrxdJI6eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGLoNVgh[2WubIO= MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
EGFR / c-Met / IGF-1Rβ/ Akt / p-Akt / ERK / p-ERK; 

PubMed: 23418523     


Downregulation of multiple signaling pathways by ganetespib in melanoma cells.A. Cells were treated with indicated amounts of ganetespib for 24 h. B-RAF and N-RAS mutational status of each cell line is indicated.

p27(Kip1) / p21 (Cip1) / Cyclin D1 / Cyclin E / Cyclin B1 / CDK1 / CDK2 / CDK4; 

PubMed: 23418523     


Alterations in expression of multiple cell cycle regulating proteins induced by ganetespib. Cells were treated with indicated amounts of ganetespib for 48 h and analyzed by Western blot analysis. Relative expression levels of proteins (treated vs. control䲧疝Ỵ疞㧀疜膉痘 

Survivin / Bcl-2 / Bcl-xl / Mcl-1; 

PubMed: 23418523     


Effect of ganetespib on the expression of antiapoptotic proteins. Cells were treated with ganetespib for 48 h and analyzed using Western blot analysis. Relative expression levels of proteins are indicated.

B-RAF / C-RAF / N-RAS ; 

PubMed: 23418523     


Effect of ganetespib on B-RAF, C-RAF and N-RAS expression in melanoma cells.Cells were treated with indicated amounts of ganetespib for 48 h and subjected to Western blot analysis.

HER2 / p-STAT3 / BIM ; 

PubMed: 25077897     


NCI-H1975 cells were incubated with the indicated concentrations of ganetespib for 24 h. Cell lysates were analyzed by Western blotting.

CDK1 / Cyclin D1 / Cyclin B1 / p27; 

PubMed: 29717218     


Cropped Western blot images of the indicated cell cycle regulators are shown in ganetespib-treated (0–300 nM for 16 hours) BT474 and SKBR3 cells. 

c-PARP / c-caspase 3 / caspase 8 / c-caspase 8 / caspase 9 / c-caspase 9; 

PubMed: 29717218     


Cropped images of Western blots at the target molecular weights for the indicated apoptotic markers are shown in ganetespib-treated (0, 10, 30, 100, 300 nM for 16 hours) BT474 and SKBR3 cells. 

ErbB2 / pErbB2 / Src / pSrc / mTOR / pmTOR / Bad / pBad / GSK3 / pGSK3; 

PubMed: 29717218     


Ganetespib inhibits RTK signaling in ErbB2+ breast cancer cells. BT474 and SKBR3 cells were treated with ganetespib (0, 10, 30, 100, or 300 nM) for 16 hours, followed by Western blot analysis (cropped images) of the expression and activation/phosphorylati䲧疝Ỵ疞㧀疜膉痘 瘿뙠ෆᾰƌෆĀ 㺣痖帉痖

Wee1 / p-Wee1 / Chk1 / p-Chk1; 

PubMed: 27834954     


Hsp90 inhibition degrades the G2/M checkpoint kinases Wee1 and Chk1. The cells were treated with 200 nM ganetespib and 75 μM carboplatin for 24 h followed by immunoblot analysis. Carboplatin treatment leads to the activation of Chk1, indicated by phospho—䲧疝Ỵ疞㧀疜膉痘 瘿삨ՂᾰƌՂĀ 㺣痖帉痖Ѐ瑖堘𢡄빢᎒ՂĀ鑸᎒彿堙奋堙巫堙᎒ﻺ᎒彿堙ﻮ᎒塚堙ﻺ᎒ꍈ堞빢᎒學堙漸堞圔堙빢᎒圞堙圭堙𢡄玚Wᾰƌ ᾰƌ

23418523 25077897 29717218 27834954
Growth inhibition assay
Cell viability ; 

PubMed: 23418523     


A. Ganetespib reduced viability. Cells were treated with varying amounts of ganetespib for 72 h and subjected to MTS assay. Data are expressed as mean±SD of three independent experiments. B. Mutational status and ganetespib IC50 of cell lines.

23418523
In vivo Administration of Ganetespib leads to significant tumor shrinkage in several tumor xenograft models in mice and appears to be less toxic. Furthermore Ganetespib demonstrated better tumor penetration compared with tanespimycin.[2] Ganetespib inhibits in vivo tumor growth in both malignant mast cell and OSA xenograft models. Ganetespib significantly inhibits tumor growth when dosed with two repeating cycles of 25 mg/kg/day for 3 days, with a %T/C value of 18. Ganetespib is well-tolerated, with the vehicle and Ganetespib groups having average bodyweight changes relative to the start of the study of +0.3% and -8.1% on day 17, respectively.[4]

Protocol

Cell Research:[1]
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  • Cell lines: OSA cells
  • Concentrations: 0.001-1μM
  • Incubation Time: 5 days
  • Method: A total of 1.5 × 103 OSA cells are seeded in 96-well plates in 10% serum-containing complete medium and incubated overnight to determine the 50% inhibitory concentrations. Plates are, harvested at day 5 following 0.001, 0.005, 0.01, 0.05, 0.1, 0.5 and 1 μM Ganetespib, treatment and analyzed. Fluorescence measurements are made using a plate reader with excitation at 485 nm and emission detection at 530 nm. Relative cell number is calculated as a percentage of the control wells: absorbance of sample/absorbance of DMSO treated cells × 100.
    (Only for Reference)
Animal Research:[4]
- Collapse
  • Animal Models: Female severe combined immune-deficient (SCID) mice
  • Dosages: 25 mg/kg/day for 3 days
  • Administration: Tail vein injection
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 40 mg/mL (109.76 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
5% DMSO+45% PEG 300+ddH2O
For best results, use promptly after mixing.
11mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 364.4
Formula

C20H20N4O3

CAS No. 888216-25-9
Storage powder
in solvent
Synonyms N/A
Smiles CC(C)C1=C(C=C(C(=C1)C2=NNC(=O)N2C3=CC4=C(C=C3)N(C=C4)C)O)O

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
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Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

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*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and SDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

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  • C1=C0/X C1: LOG(C1):
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Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02192541 Terminated Drug: Ziv-Aflibercept|Drug: Ganetespib Neoplasms National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) December 2 2014 Phase 1
NCT02008877 Completed Drug: ganetespib|Drug: Sirolimus Malignant Peripheral Nerve Sheath Tumors (MPNST)|Sarcoma Sarcoma Alliance for Research through Collaboration|Synta Pharmaceuticals Corp.|United States Department of Defense December 2013 Phase 1|Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

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Frequently Asked Questions

  • Question 1:

    Does this inhibitor inhibit both isoforms of HSP90?

  • Answer:

    We don't have the information now and it is not very clear in the literature either. From following two references, it indicates that Ganetespib might be specific to the alpha form “Ganetespib binds to the ATP binding site of Hsp90 alpha with a Kd of 110 nM” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477583/

HSP (HSP90) Signaling Pathway Map

HSP (HSP90) Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID