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NMS-E973
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
NMS-E973图片
CAS NO:1253584-84-7
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)454.43
FormulaC22H22N4O7
CAS No.1253584-84-7
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 90 mg/mL (198.1 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
SMILESO=C(C1=NOC(C2=C(OC3=CC=C([N+]([O-])=O)C=C3)C=C(O)C=C2O)=C1)NC4CCN(C)CC4
SynonymsNMSE973; NMS E973; NMS-E973;
实验参考方法
In Vitro

In vitro activity: NMS-E973 shows a widespread antiproliferative activity with an average IC50 of 1.6 μM, and induces the degradation of client protein, such as Flt3, B-Raf, AKT, which further blocks tumor-related pathways, such as the Raf/MAPK, PI3K/AKT, and JAK/STAT pathways.


Kinase Assay: For competition experiments, a protein concentration of 5 nM for Hsp90 and of 200 nM for Trap1 are mixed with 0.5 nmol/L probe (final concentrations). After incubation, the dimethyl sulfoxide (DMSO) compound solution is added to the mixture. The plate is incubated for 18 hours at room temperature and then the fluorescence polarization signal was measured. Data are fitted with the program Dynafit version 3.28.039 or SigmaPlot (SSI) using the mathematical equation for competitive binding of 2 ligands to the receptor.


Cell Assay: NMS-E973 is a potent and selective Hsp90 inhibitor with DC50 of<10 nM for Hsp90 binding, no activiy against a panel of 52 diverse protein kinases. NMS-E973 exerts antiproliferation effects on A2780 tumor cell line and BT-474 breast cancer cell line with IC50 values of 69nM and 110nM, respectively. When treated with mice bearing A2780 xenografts, the intravenous administration of NMS-E973 significantly inhibits tumor growth with TGI value of 53% at dose of 30mg/kg.

In VivoNMS-E973 (10 mg/kg i.v.) shows a favorable pharmacokinetic profile with selective retention in tumor tissue and ability to cross the BBB. NMS-E973 (60 mg/kg i.v.) shows high antitumor efficacy in all the models tested, including A375 and A2780 xenografts. In addition, NMS-E973 (10 mg/kg i.v.) together with B-Raf inhibitor PLX-4720 at 100 mg/kg produces a synergic anti-tumor effect. In a mouse model of human ovarian cancer, NMS-E973 produces the antitumor activity by inhibition of Hsp90.
Animal modelMice bearing A375 xenografts, A2780 xenografts, MOLM-13 xenografts or RKO xenografts.
Formulation & DosageDissolved in 10% Tween 80 in 5% dextrose solution; 60 mg/kg; i.v.
ReferencesClin Cancer Res. 2013 Jul 1;19(13):3520-32; Bioorg Med Chem. 2013 Nov 15;21(22):7047-63.