Luminespib (AUY-922, NVP-AUY922) 747412-49-3

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Molecular Weight: 465.54 Luminespib (AUY-922, 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 2.


Biological Activity


NVP-AUY922 inhibits proliferation of various human cancer cell lines in vitro, with an average GI50 of 9 nM.
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. 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.


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



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.
Solubility	1% DMSO/30% polyethylene glycol/1% Tween 80, 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.

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

Species	Baboon	Dog	Monkey	Rabbit	Guinea pig	Rat	Hamster	Mouse
Weight (kg)	12	10	3	1.8	0.4	0.15	0.08	0.02
Body Surface Area (m2)	0.6	0.5	0.24	0.15	0.05	0.025	0.02	0.007
Km factor	20	20	12	12	8	6	5	3

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)

Chemical Information

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

Storage	3 years -20℃Powder
	6 months-80℃in solvent (DMSO, water, etc.)
Synonyms	VER-52296

Solubility (25°C) *	In vitro	DMSO	93 mg/mL heating (199.76 mM)
		Water	<1 mg/mL (
		Ethanol	31 mg/mL (66.58 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

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Product Categories : Cytoskeletal Signaling > HSP Inhibitor