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NMS-E973 HSP inhibitor

Cat.No.S7282

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 HSP inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 454.43

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability

Quality Control

Batch: S728201 DMSO]90 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.07%
99.07

Chemical Information, Storage & Stability

Molecular Weight 454.43 Formula

C22H22N4O7

 Storage (From the date of receipt)
CAS No. 1253584-84-7 -- Storage of Stock Solutions

Synonyms N/A Smiles CN1CCC(CC1)NC(=O)C2=NOC(=C2)C3=C(C=C(C=C3OC4=CC=C(C=C4)[N+](=O)[O-])O)O

Solubility

In vitro
Batch:

DMSO : 90 mg/mL (198.05 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC50/Ki
HSP90 [1]
<10 nM(DC50)
In vitro
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. [1]
Kinase Assay
Hsp90 binding assays
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.
In vivo
NMS-E973 (10 mg/kg i.v.) shows a favorable pharmacokinetic profile with selective retention in tumor tissue and ability to cross the BBB. This compound (60 mg/kg i.v.) shows high antitumor efficacy in all the models tested, including A375 and A2780 xenografts. In addition, this chemical (10 mg/kg i.v.) together with B-Raf inhibitor PLX-4720 at 100 mg/kg produces a synergic anti-tumor effect. [1] In a mouse model of human ovarian cancer, it produces the antitumor activity by inhibition of Hsp90. [2]
References

Applications

Methods Biomarkers Images PMID
Growth inhibition assay Cell viability S7282-viability1 29593424
Western blot PUMA / NOXA / BID / BAD / Bak / Bmf S7282-WB1 29593424

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