AUY922 (NVP-AUY922)

貨號 Cat. No.: S1069
規格 Size: 5~200mg
品牌 Brand: Selleckchem

Description

AUY922 (NVP-AUY922)

Catalog No.S1069

1 Reviews 6 Product Citations

AUY922 (NVP-AUY922) is a highly potent HSP90 inhibitor for HSP90α/β with IC50 of 13 nM /21 nM, weaker potency against the HSP90 family members GRP94 and TRAP-1, exhibits the tightest binding of any small-molecule HSP90 ligand. Phase 1/2.

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10mM/1mLIn DMSO	USD 403	In stock	0 1 2 3 4 5 6 7 8 9 10
5mg	USD 201	In stock	0 1 2 3 4 5 6 7 8 9 10
10mg	USD 340	In stock	0 1 2 3 4 5 6 7 8 9 10
25mg	USD 592	In stock	0 1 2 3 4 5 6 7 8 9 10
200mg	USD 2142	In stock	0 1 2 3 4 5 6 7 8 9 10

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

Biological Activity

Description	AUY922 (NVP-AUY922) is a highly potent HSP90 inhibitor for HSP90α/β with IC50 of 13 nM /21 nM, weaker potency against the HSP90 family members GRP94 and TRAP-1, exhibits the tightest binding of any small-molecule HSP90 ligand. Phase 1/2.
Targets	HSP90α	HSP90β
IC50	13 nM	21 nM ^[1]
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 PDGFRÉ‘ 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]
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
Dosages	50 mg/kg
Administration	Administered via i.v. or i.p.
Solubility	1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL

References

Clinical Trial Information( data from http://clinicaltrials.gov)

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT01752400	Recruiting	Non Small Cell Lung Cancer	Massachusetts General Hospital	2013-01	Phase 2
NCT01772797	Recruiting	Anaplastic Lymphoma Kinase (ALK)\|Non-small Cell Lung Cancer	Novartis\|Novartis Pharmaceuticals	2013-06	Phase 1
NCT01854034	Recruiting	Non Small Cell Lung Cancer	Massachusetts General Hospital	2013-07	Phase 2
NCT01922583	Not yet recruiting	Non-small Cell Lung Cancer (NSCLC)	National Taiwan University Hospital	2013-12	Phase 2
NCT01784640	Not yet recruiting	Recurrent Non-small Cell Lung Cancer\|Squamous Cell Lung Cancer\|Stage IV Non-small Cell Lung Cancer	Jonsson Comprehensive Cancer Center\|National Cancer Institute (NCI)	2014-01	Phase 1

Chemical Information

Download AUY922 (NVP-AUY922) SDF

Molecular Weight (MW)	465.54
Formula	C₂₆H₃₁N₃O₅
CAS No.	747412-49-3

Storage	3 years -20â„ƒPowder
Storage	6 months-80â„ƒin DMSO
Syonnyms	N/A

Solubility (25°C) *	In vitro	DMSO	93 mg/mL (199 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	93 mg/mL (199 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

Preparing Stock Solutions

Stock Solution (1ml DMSO)	1mM	10mM	20mM	30mM
Mass(mg)	0.46554	4.6554	9.3108	13.9662

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Customer Reviews (1)

Click to enlarge	Rating
	Source	Dr Swee Sharp and Professor Paul Workman from Cancer Research UK. AUY922 (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.