Luminespib (NVP-AUY922)

For research use only.

Catalog No.S1069 Synonyms: AUY-922

78 publications

Luminespib (NVP-AUY922) Chemical Structure

CAS No. 747412-49-3

Luminespib (AUY-922, NVP-AUY922) is a highly potent HSP90 inhibitor for HSP90α/β with IC50 of 13 nM /21 nM in cell-free assays, weaker potency against the HSP90 family members GRP94 and TRAP-1, exhibits the tightest binding of any small-molecule HSP90 ligand. Luminespib (AUY-922, NVP-AUY922) effectively downregulates and destabilizes the IGF-1Rβ protein and results in growth inhibition, autophagy and apoptosis. Phase 2.

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Selleck's Luminespib (NVP-AUY922) has been cited by 78 publications

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Choose Selective HSP (HSP90) Inhibitors

Biological Activity

Description Luminespib (AUY-922, NVP-AUY922) is a highly potent HSP90 inhibitor for HSP90α/β with IC50 of 13 nM /21 nM in cell-free assays, weaker potency against the HSP90 family members GRP94 and TRAP-1, exhibits the tightest binding of any small-molecule HSP90 ligand. Luminespib (AUY-922, NVP-AUY922) effectively downregulates and destabilizes the IGF-1Rβ protein and results in growth inhibition, autophagy and apoptosis. Phase 2.
Targets
HSP90α [1]
(Cell-free assay)
HSP90β [1]
(Cell-free assay)
13 nM 21 nM
In vitro

NVP-AUY922 inhibits proliferation of various human cancer cell lines in vitro, with an average GI50 of 9 nM. [1] The IC50 values of NVP-AUY922 fall in the range of 2 to 40 nM in these gastric cancer cell lines. IC50 value for the BEAS-2B cells is 28.49 nM. Treatment with NVP-AUY922 does not influence the expression of HSP90, but expression of HSP70 gets elevated by NVP-AUY922 treatment. NVP-AUY922 increases the binding of HSP70 to HSP90. NVP-AUY922 causes p23 dissociation from the HSP90 complex and can then recruit HSP70 to the HSP90 complex. [1] After the treatment with NVP-AUY922, expression of receptor tyrosine kinases including VEGFR1, 2, 3 and PDGFRɑ is decreased. A decrease is also noticed in the expression of Akt and phospho-Akt. Meanwhile, treatment with NVP-AUY922 causes decreased expression of HER-2 in NCI-N87 cells. NVP-AUY922 treatment results in binding of HSP90 to client proteins and setting them up as targets for degradation by the proteasome. NVP-AUY922 can influence cell growth by affecting multiple signaling pathways. In addition, treatment with the proteasome inhibitor, MG132, restores expression of thymidylate synthase, which is decreased by NVP-AUY922. NVP-AUY922 increases the expression of cleaved caspase-3 leading to apoptosis in HSC-2 cells.[1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NCI-SNU-16 NYPjO41YT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYXJR|UxRTR6LkOxOFIh|ryP NH7mOZE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPTJzNkSvK|5USU6JRWK8M4E,
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NCI-H82 NYr1VJZlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYXJR|UxRTJ|LkW1NlYh|ryP MkDjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlUzOTZ2Lze+V2FPT0WUPD;hQi=>
RT4 Mn3MS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTDeGRlUUN3ME2yN{4{Ojh{IN88US=> M4HVXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI2OjF4ND:nQnNCVkeHUkyvZV4>
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LC-1F MkPUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX7JR|UxRTZwMEmyPVEh|ryP M{GzflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI2OjF4ND:nQnNCVkeHUkyvZV4>
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OAW-42 MofuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mo\3TWM2OD1yLkCzO|Q4KM7:TR?= Mkj2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlUzOTZ2Lze+V2FPT0WUPD;hQi=>
HCC38 NIe1WJJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3fUTGlEPTB;MD6wN|c4OSEQvF2= MnHIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlUzOTZ2Lze+V2FPT0WUPD;hQi=>
Calu-3 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV3JR|UxRTBwMEO3PFkh|ryP MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyOVIyPjRxJ{7TRW5ITVJ:L3G+
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KYSE-70 MoLqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkSxTWM2OD1yLkCzPFEzKM7:TR?= M171XFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI2OjF4ND:nQnNCVkeHUkyvZV4>
OVCAR-4 MnrES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGr5ZYZKSzVyPUCuNFM5PThizszN MmjyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlUzOTZ2Lze+V2FPT0WUPD;hQi=>
D-392MG MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4f3UGlEPTB;MD6wN|g1OiEQvF2= NFfCdmQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPTJzNkSvK|5USU6JRWK8M4E,
HEL M1:0fGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnLTTWM2OD1yLkCzPFkyKM7:TR?= NGCzSlY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPTJzNkSvK|5USU6JRWK8M4E,
Detroit562 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWTJR|UxRTBwMEO4O|Ih|ryP NE\JbGM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPTJzNkSvK|5USU6JRWK8M4E,
MONO-MAC-6 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkPQTWM2OD1yLkCzPFk{KM7:TR?= MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyOVIyPjRxJ{7TRW5ITVJ:L3G+
LoVo NFTTWoZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW[ybIg{UUN3ME2wMlA{QTN|IN88US=> NGTQ[4M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPTJzNkSvK|5USU6JRWK8M4E,
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A172 NFn1dFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGnnNVRKSzVyPUCuNFM6PSEQvF2= NID3NmM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPTJzNkSvK|5USU6JRWK8M4E,
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SW48 NFjMdohIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmfNTWM2OD1yLkC0NFMyKM7:TR?= MmrYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlUzOTZ2Lze+V2FPT0WUPD;hQi=>
HC-1 MkS3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnS3TWM2OD1yLkC0NFY6KM7:TR?= NXfJdZJERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjV{MU[0M{c,W0GQR1XSQE9iRg>?
HDLM-2 MnHrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NULFZoZOUUN3ME2wMlA1OTF2IN88US=> M{\IRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI2OjF4ND:nQnNCVkeHUkyvZV4>
KOSC-2 M33ZbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NETmcllKSzVyPUCuNFQyOSEQvF2= NIfwbGk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPTJzNkSvK|5USU6JRWK8M4E,
CTV-1 M1L2S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYjaWXN3UUN3ME2wMlA1OTF4IN88US=> M{S0fVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI2OjF4ND:nQnNCVkeHUkyvZV4>
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SW756 MkHxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUO2VohDUUN3ME2wMlA1OTV5IN88US=> NH3adYc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPTJzNkSvK|5USU6JRWK8M4E,
GCT Mm[xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkDmTWM2OD1yLkC0NVYyKM7:TR?= NWHnRVU{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjV{MU[0M{c,W0GQR1XSQE9iRg>?
CHL-1 M4TiWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUm4c3FrUUN3ME2wMlA1OTZ7IN88US=> MmSzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlUzOTZ2Lze+V2FPT0WUPD;hQi=>
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LAMA-84 Mk[wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYT5N3RRUUN3ME2wMlA1OTdzIN88US=> M2LqflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI2OjF4ND:nQnNCVkeHUkyvZV4>
NCI-H358 MlKzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{O2PGlEPTB;MD6wOFIyOiEQvF2= NUDVWIFxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjV{MU[0M{c,W0GQR1XSQE9iRg>?
NB13 NIDBbGFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlK5TWM2OD1yLkC0NlI4KM7:TR?= MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyOVIyPjRxJ{7TRW5ITVJ:L3G+
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-ALK / ALK / p-AKT / AKT / p-ERK / ERK / TβRI / TβRII; 

PubMed: 23993685     


Cells were treated with or without the indicated doses of 17-DMAG or AUY-922 for 3 h. Changes in ALK-related signaling and TGF-b receptors were analyzed using Western blot analysis. The densitometry values were determined relative to control of H2228 after normalization to b-actin protein.

E-cadherin / Cleaved PARP / Bim; 

PubMed: 23993685     


Cells were treated with crizotinib (1 mM), 17-DMAG (1 mM), or AUY-922 (1 mM) for the indicated times. Cell lysates were subjected to Western blot analysis using the indicated antibodies. The densitometry values were determined relative to control after normalization to b-actin protein.

HSP70 / Grp94 / Grp78 / p-eIF2α / CHOP / IRE1α / p-JNK; 

PubMed: 24796583     


CCA cells were incubated with 0.5 uM NVP-AUY922 for 0, 2, 4, 8, 16, and 24 h. Whole cell lysates were subjected to western blot analysis for HSP70, Grp94, Grp78, p-eIF2α, CHOP, IRE1α, and phosphor-JNK. β-Actin was used as the loading control.

CDK4 / HMGA2 ; 

PubMed: 26893968     


HCT116 cells were treated with NVP-AUY922 at the indicated concentrations for 48 hours. Cell extracts were analyzed using Western blotting with the antibodies for CDK4, Hsp70, and HMGA2, respectively.

23993685 24796583 26893968
Growth inhibition assay
Cell viability; 

PubMed: 26893968     


Cell viability assay was performed to determine the of HCT116 cells treated with various concentrations of NVP-AUY922 for 48 hours. *p < 0.05, **p < 0.01, ***p < 0.001. All experiments were performed in three independent experiments.

26893968
In vivo Treatment with NVP-AUY922 causes a robust antitumor response and inhibits p-Akt and VEGF expression in an HSC-2 xenograft model. [2] In BT474, NVP-AUY922 shows complete loss of ERBB2 and substantial depletion of ERα, in addition to reductions in CDK4 and phospho-ERK1/2. [3]

Protocol

Kinase Assay:[3]
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Kinase assay:

NVP-AUY922 is dissolved in DMSO at a concentration of 10 mM. NVP-AUY922 is assessed against HSP90α, HSP90β, GRP94, TRAP-1, HSP72, and topoisomerase II. Profiling against a panel of kinases has been carried out and screening against a panel of additional enzymes and receptors is performed at Cerep.
Cell Research:[1]
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  • Cell lines: Human gastric cancer cells NCI-N87
  • Concentrations: 1 μM
  • Incubation Time: 3 days
  • Method: Human gastric cancer cells NCI-N87 (5-7 ×103 in 50 μL/well) are seeded in 96-well plates and incubated at 37 °C for 24 hours, followed by NVP-AUY922 treatment for 1-3 days at 37 °C. After treatment, the cells are assayed by MTT method and analyzed by microplate reader.
    (Only for Reference)
Animal Research:[3]
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  • Animal Models: Female NCr athymic mice bearing WM266.4 human melanoma xenografts
  • Dosages: 50 mg/kg
  • Administration: Administered via i.v. or i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 93 mg/mL warmed (199.76 mM)
Ethanol 31 mg/mL (66.58 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
1% DMSO+30% polyethylene glycol+1% Tween 80
For best results, use promptly after mixing.
30 mg/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 465.54
Formula

C26H31N3O5

CAS No. 747412-49-3
Storage powder
in solvent
Synonyms AUY-922
Smiles CCNC(=O)C1=NOC(=C1C2=CC=C(C=C2)CN3CCOCC3)C4=CC(=C(C=C4O)O)C(C)C

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 ()
% DMSO % % Tween 80 % ddH2O
CalculateReset

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)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / 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 )

  • C1
    V1
    C2
    V2

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

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
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
NCT01772797 Completed Drug: LDK378|Drug: AUY922 Anaplastic Lymphoma Kinase (ALK)|Non-small Cell Lung Cancer Novartis Pharmaceuticals|Novartis June 2013 Phase 1
NCT01752400 Completed Drug: AUY922 Non Small Cell Lung Cancer Massachusetts General Hospital January 2013 Phase 2
NCT01613950 Completed Drug: AUY922|Drug: BYL719 Stomach Neoplasms Esophageal Neoplasms Metastatic Gastric Cancer Mutated PI3KCA Protein Overexpressed HER2 Protein Novartis Pharmaceuticals|Novartis December 2012 Phase 1
NCT01484860 Terminated Drug: AUY922 Adenocarcinoma of the Pancreas|Metastatic Disease University Health Network Toronto|Novartis Pharmaceuticals January 2012 Phase 2
NCT01402401 Terminated Drug: AUY922|Drug: Trastuzumab Advanced Gastric Cancer Novartis Pharmaceuticals|Novartis November 2011 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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID