Ganetespib (STA-9090)

Catalog No.S1159

For research use only.

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.

Ganetespib (STA-9090) Chemical Structure

CAS No. 888216-25-9

Selleck's Ganetespib (STA-9090) has been cited by 47 publications

Purity & Quality Control

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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 MkHqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHjuS3c4OiCq MXPJR|UxRThibl2= MoPxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzNES2OlUoRjJ{MUS0OlY2RC:jPh?=
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Calu-6 MkXYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF:wN3ZKSzVyPU[0JI5O NYL6cYV5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwNVIzPDhpPkKzNFEzOjR6PD;hQi=>
Calu-1 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M17DcGlEPTB;NUigcm0> NVnmVVFQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwNVIzPDhpPkKzNFEzOjR6PD;hQi=>
H2122 M{\jO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWnJR|UxRTV|IH7N NHvI[Zg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{CxNlI1QCd-MkOwNVIzPDh:L3G+
A549 MnjUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NELBW4ZKSzVyPUSzJI5O Mnf3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjNyMUKyOFgoRjJ|MEGyNlQ5RC:jPh?=
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K028 M3rv[mZ2dmO2aX;uJGF{e2G7 M3fSNlI2OCCwTR?= M3zWZlI1KGh? M2POTIlv\HWlZYOgS|Ih[XK{ZYP0 M4DQeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NEG4OVI{Lz5{M{SxPFUzOzxxYU6=
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H146 NF;GR2FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIizXG9KSzVyPUK4MlUyKG6P MnrWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzNk[1NFUoRjJ2MU[2OVA2RC:jPh?=
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LS-123 NVLEVpM1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn;lTWM2OD15MzDuUS=> NIfj[YM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NE[4Nlc1Pyd-MkS2PFI4PDd:L3G+
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LAN-5 M4XabJFJXFNiYYPzZZk> MWDxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVEGQLUWgZ4VtdHN? MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Rh18 NGH1dmxyUFSVIHHzd4F6 MWjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmhzODDj[Yxtew>? MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Assay
Methods Test Index PMID
Western blot EGFR / c-Met / IGF-1Rβ/ Akt / p-Akt / ERK / p-ERK ; p27(Kip1) / p21 (Cip1) / Cyclin D1 / Cyclin E / Cyclin B1 / CDK1 / CDK2 / CDK4 ; Survivin / Bcl-2 / Bcl-xl / Mcl-1 ; B-RAF / C-RAF / N-RAS ; HER2 / p-STAT3 / BIM ; CDK1 / Cyclin D1 / Cyclin B1 / p27 ; c-PARP / c-caspase 3 / caspase 8 / c-caspase 8 / caspase 9 / c-caspase 9 ; ErbB2 / pErbB2 / Src / pSrc / mTOR / pmTOR / Bad / pBad / GSK3 / pGSK3 ; Wee1 / p-Wee1 / Chk1 / p-Chk1 23418523 25077897 29717218 27834954
Growth inhibition assay Cell viability 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 (from reference)

Cell Research:[1]
  • 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.
Animal Research:[4]
  • Animal Models: Female severe combined immune-deficient (SCID) mice
  • Dosages: 25 mg/kg/day for 3 days
  • Administration: Tail vein injection

Solubility (25°C)

In vitro

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

Chemical Information

Molecular Weight 364.4
Formula

C20H20N4O3

CAS No. 888216-25-9
Storage 3 years -20°C powder
2 years -80°C in solvent
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)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

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

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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

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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/

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