Luminespib (AUY-922, NVP-AUY922)

Catalog No.S1069

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. Phase 2.

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Luminespib (AUY-922, NVP-AUY922) Chemical Structure

Luminespib (AUY-922, NVP-AUY922) Chemical Structure
Molecular Weight: 465.54

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Related Compound Libraries

Luminespib (AUY-922, NVP-AUY922) is available in the following compound libraries:

HSP (e.g. HSP90) Inhibitors with Unique Features

  • Selective HSP90 Inhibitor

    NVP-BEP800 HSP90β-selective, IC50=58 nM.

  • Most Potent HSP90 Inhibitor

    KW-2478 HSP90, IC50=3.8 nM.

  • HSP90 Inhibitor in Clinical Trial

    17-AAG (Tanespimycin) Phase III for Gastrointestinal Stromal Tumors.

  • Newest HSP90 Inhibitor

    XL888 ATP-competitive inhibitor of HSP90 with IC50 of 24 nM.

Product Information

  • Compare HSP (e.g. HSP90) Inhibitors
    Compare HSP (e.g. HSP90) Products
  • Research Area
  • Luminespib (AUY-922, NVP-AUY922) Mechanism

Product Description

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. Phase 2.
Targets HSP90α [1]
(Cell-free assay)
HSP90β [1]
(Cell-free assay)
IC50 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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... Click to View More Cell Line Experimental Data

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]
Features

Protocol(Only for Reference)

Kinase Assay: [3]

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 Assay: [1]

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.

Animal Study: [3]

Animal Models Female NCr athymic mice bearing WM266.4 human melanoma xenografts
Formulation In DMSO and diluted in sterile saline/Tween 20
Dosages 50 mg/kg
Administration Administered via i.v. or i.p.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Lee KH, et al. Cancer Sci, 2011, 102(7), 1388-1395.

[2] Okui T, et al. Anticancer Res, 2011, 31(4), 1197-1204.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-23)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT01784640 Active, not recruiting Recurrent Non-small Cell Lung Cancer|Squamous Cell Lung Cancer|Stage IV Non-small Cell Lung Cancer Jonsson Comprehensive Cancer Center|National Cancer Insti  ...more Jonsson Comprehensive Cancer Center|National Cancer Institute (NCI) January 2014 Phase 1
NCT01922583 Recruiting Non-small Cell Lung Cancer (NSCLC) National Taiwan University Hospital January 2014 Phase 2
NCT01854034 Recruiting Non Small Cell Lung Cancer Massachusetts General Hospital July 2013 Phase 2
NCT01772797 Completed Anaplastic Lymphoma Kinase (ALK)|Non-small Cell Lung Cancer Novartis Pharmaceuticals|Novartis June 2013 Phase 1
NCT01752400 Active, not recruiting Non Small Cell Lung Cancer Massachusetts General Hospital January 2013 Phase 2

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Chemical Information

Download Luminespib (AUY-922, NVP-AUY922) SDF
Molecular Weight (MW) 465.54
Formula

C26H31N3O5

CAS No. 747412-49-3
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms VER-52296
Solubility (25°C) * In vitro DMSO 93 mg/mL warming (199.76 mM)
Ethanol 31 mg/mL (66.58 mM)
Water <1 mg/mL (<1 mM)
In vivo 1% DMSO+30% polyethylene glycol+1% Tween 80 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* 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 Name 5-(2,4-dihydroxy-5-isopropylphenyl)-N-ethyl-4-(4-(morpholinomethyl)phenyl)isoxazole-3-carboxamide

Customer Product Validation(3)


Click to enlarge
Rating
Source Proc Natl Acad Sci USA, 2014, 111(15): E1528–37 . Luminespib (AUY-922, NVP-AUY922) purchased from Selleck
Method Immunostaining
Cell Lines U2OS_exo cells
Concentrations 4 µM
Incubation Time 20 h
Results AUY922 blocked nuclear migration of RelA/p50 induced by TNFα in a dose-dependent manner, consistent with the notion that Hsp90 is required for activation of the NF-κB pathway.

Click to enlarge
Rating
Source J Biol Chem 2013 288(23), 16308-20. Luminespib (AUY-922, NVP-AUY922) purchased from Selleck
Method Western blot
Cell Lines 293T cells
Concentrations 1 uM
Incubation Time 16 h
Results Treatment of cellswith each of these HSP90 inhibitors (17-AAG, SNX-5422, or NVP-AUY922) caused a significant reduction in TSSK1, -2, -4, and -6 in the cells.

Click to enlarge
Rating
Source 2011 Dr. Swee Sharp and Professor Paul Workman from Cancer Research UK. Luminespib (AUY-922, NVP-AUY922) purchased from Selleck
Method Western blot
Cell Lines BT474 breast cancer cell line
Concentrations 1.0 ± 0.1 nM
Incubation Time 8/24 h
Results Western blots show the molecular signature of HSP90 inhibition by NVP-AUY922.

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.

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
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