NVP-BEP800

製品コードS1498 バッチS149801

印刷

化学情報

Chemical Structure Synonyms VER82576 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C21H23Cl2N5O2S
分子量 480.41 CAS No. 847559-80-2
Solubility (25°C)* 体外 Ethanol 15 mg/mL (31.22 mM)
DMSO Insoluble
Water Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
in vitro NVP-BEP800 is an ATP-competitive inhibitor of Hsp90β with an IC50 of 58 nM, exhibiting >70-fold selectivity against Hsp90 family members Grp94 and Trap-1 with IC50 values of 4.1 μM and 5.5 μM, 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 μM. NVP-BEP800 potently inhibits the proliferation of various tumor cell lines with GI50 values ranging from 38 nM in A375 to 1.05 μM in PC3, and primary human tumors with the mean IC50 of 0.75 μM and IC70 of 1.8 μM. 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]

プロトコル(参考用のみ)

キナーゼアッセイ Competitive binding fluorescent polarization assay
Recombinant Hsp90β, 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 Hsp90β by NVP-BEP800. The concentration of NVP-BEP800 which inhibits Hsp90β by 50% is determined from the competition curve.
細胞アッセイ 細胞株 A375, PC3, A2058, A549, HCT116, BT-474, SKBr3, MCF-7, MDAMB-157, MDA-MB-231, MDA-MB-468, and BT20
濃度 Dissolved in DMSO as a 10 mM stock solution, final concentrations ~1 mM
反応時間 24 hours
実験の流れ 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.
動物実験 動物モデル Female Harlan HsdNpa: Athymic Nude-nu mice injected s.c. with BT-474 or A375 cells
投薬量 ~50 mg/kg/day
投与方法 Orally

カスタマーフィードバック

Data from [Cancer Cell, 2012, 20(3), 400-13]

, , Dr. Swee Sharp and Professor Paul Workman from Cancer Research UK

Data from [Data independently produced by , , Mol Cancer, 2017, 16(1):72]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

HSP90 inhibitor NVP-BEP800 affects stability of SRC kinases and growth of T-cell and B-cell acute lymphoblastic leukemias [ Blood Cancer J, 2021, 11(3):61] PubMed: 33737511
The HSP GRP94 interacts with macrophage intracellular complement C3 and impacts M2 profile during ER stress [ Cell Death Dis, 2021, 12(1):114] PubMed: 33483465
The HSP GRP94 interacts with macrophage intracellular complement C3 and impacts M2 profile during ER stress [ Cell Death Dis, 2021, 12(1):114] PubMed: 33483465
Hsp90 Inhibitor STA9090 Sensitizes Hepatocellular Carcinoma to Hyperthermia-Induced DNA Damage by Suppressing DNA-PKcs Protein Stability and mRNA Transcription [ Mol Cancer Ther, 2021, 10.1158/1535-7163.MCT-21-0215] PubMed: 34376581
The Global Phosphorylation Landscape of SARS-CoV-2 Infection [ Cell, 2020, 182(3):685-712.e19] PubMed: 32645325
The Global Phosphorylation Landscape of SARS-CoV-2 Infection [ Cell, 2020, 182(3):685-712.e19] PubMed: 32645325
Hsp90 inhibitor HSP990 in very low dose upregulates EAAT2 and exerts potent antiepileptic activity [ Theranostics, 2020, 10(18):8415-8429] PubMed: 32724478
Human Mesenchymal Stem Cell Secretome from Bone Marrow or Adipose-Derived Tissue Sources for Treatment of Hypoxia-Induced Pulmonary Epithelial Injury. [ Int J Mol Sci, 2018, 19(10)] PubMed: 30274394
Hsp90β promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma. [Meng J, et al. Mol Cancer, 2017, 16(1):72] PubMed: 28359326
Identification of HSP90 inhibitors as a novel class of senolytics. [ Nat Commun, 2017, 8(1):422] PubMed: 28871086

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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