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NVP-BEP800

NVP-BEP800

Item no.	S1498-50
Manufacturer	Selleckchem
CASRN	847559-80-2
Amount	50 mg
Quantity options	10 mg 200 mg 5 mg 50 mg
Category	Oncology Neuroscience Neuroinflammation Metabolism Cholesterol & Lipid Metabolism Protein Aggregation, Clearance & Misfolding Enzymes Other Fatty Acid Enzymes Inhibitors & Compound Libraries Small Molecules By Organ Lung Cancer Skin Cancer Breast Cancer
Type	Inhibitors
Specific against	other
Smiles	CCNC(=O)C1=CC2=C(N=C(N=C2S1)N)C3=CC(=C(C=C3Cl)Cl)OCCN4CCCC4
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	VER82576
Similar products	NVP-BEP800
Available
Storage Conditions	2 years -80 in solvent
Molecular Weight	480, 41
Administration	Orally
Animal Models	Female Harlan HsdNpa: Athymic Nude-nu mice injected s.c. with BT-474 or A375 cells
Cell lines	A375, PC3, A2058, A549, HCT116, BT-474, SKBr3, MCF-7, MDAMB-157, MDA-MB-231, MDA-MB-468, and BT20
Concentrations	Dissolved in DMSO as a 10 mM stock solution, final concentrations ca.1 mM
Dosages	ca.50 mg/kg/day
Formulation	Formulated as a suspension in 0.5% methyl cellulose
IC50	58 nM [1], 58 nM [1], 58 nM [1], 58 nM [1], 58 nM [1], 58 nM [1]
In vitro	NVP-BEP800 is an ATP-competitive inhibitor of Hsp90beta with an IC50 of 58 nM, exhibiting >70-fold selectivity against Hsp90 family members Grp94 and Trap-1 with IC50 values of 4.1 uM and 5.5 uM, respectively. NVP-BEP800 displays no inhibitory activity against the closely related GHKL ATPase, topoisomerase II, and the structurally unrelated ATPase, Hsp70 at the concentration of 10 uM. NVP-BEP800 potently inhibits the proliferation of various tumor cell lines with GI50 values ranging from 38 nM in A375 to 1.05 uM in PC3, and primary human tumors with the mean IC50 of 0.75 uM and IC70 of 1.8 uM. NVP-BEP800 treatment at the concentration of five times the GI50 increases the percentage of G2-M phase in A2058 and A549 cells and sub-G1 phase in BT-474, HCT116, A2058 and A549 cells by 29.5%, 33.6%, 42.7%, 12.1%, 5.9% and 7.1%, respectively. NVP-BEP800 treatment causes Akt and ErbB2 dephosphorylation, ErbB2 degradation, and Hsp70 induction in a concentration-dependent manner in BT-474 cells with IC50 values of 218 nM, 39.5 nM, 137 nM and 207 nM, respectively. [1]
In vivo	Oral administration of NVP-BEP800 at 15 or 30 mg/kg/day for 15 days causes a dose-dependent reduction in B-Raf and Akt phosphorylation levels, and displays significant dose-dependent antitumor efficacy in the A375 melanoma xenograft model with the T/C values of 53% and 6% at the dose of 15 and 30 mg/kg/day, respectively, suggesting almost complete tumor inhibition at 30 mg/kg/day. Administration of NVP-BEP800 induces dose-dependent increase of Hsp90-p23 complex dissociation and reductions in the levels of steady-state ErbB2, phospho-Akt and phospho-S6, in BT-474 breast cancer xenografts, and exhibits significant antitumor activity with 38% tumor regression at dose of 30 mg/kg/day and a T/C of 36% at dose of 15 mg/kg/day. [1]
Incubation Time	24 hours
Kinase Assay	Competitive binding fluorescent polarization assay, Recombinant Hsp90beta, TAMRA-radicicol, or various concentrations of NVP-BEP800 is added in assay buffer (50 mM TRIS pH 7.4, 5 mM MgCl2, 150 mM KCl, and 0.1% CHAPS), mixed, and incubated at room temperature for 30 to 45 minutes prior to reading. The 2D-FIDA-based HTS assay based on confocal technologies monitors the decreased fluorescence polarization on displacement of the high affinity ligand TAMRA-radicicol from Hsp90beta by NVP-BEP800. The concentration of NVP-BEP800 which inhibits Hsp90beta by 50% is determined from the competition curve.
Method	Cells are exposed to NVP-BEP800 for 24 hours. Cell proliferation is determined using either sulforhodamine B for adherent cells or MTS assay for suspension cells or those showing low adherence. Cell death is determined using a ToxiLight nondestructive cytotoxicity bioassay kit. Cell cycle progression is determined by RNase A/propidium iodide staining following fixation in 70% ethanol. Caspase-3/7 activity is determined using a homogeneous caspase activity kit.
Solubility (25C)	DMSO <1 mg/mL, Water <1 mg/mL, Ethanol 15 mg/mL
Information	NVP-BEP800 (VER82576) is a novel, fully synthetic HSP90β inhibitor with IC50 of 58 nM, exhibits>70-fold selectivity against Hsp90 family members Grp94 and Trap-1.
Chemical Name	2-amino-4-(2, 4-dichloro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-N-ethylthieno[2, 3-d]pyrimidine-6-carboxamide

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S1498-50-safety-datasheet.pdf