NMS-E973

Catalog No.S7282 Batch:S728201

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Technical Data

Formula

C22H22N4O7
Molecular Weight 454.43 CAS No. 1253584-84-7
Solubility (25°C)* In vitro DMSO 90 mg/mL (198.05 mM)
Water Insoluble
Ethanol 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description 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.
Targets
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]
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. 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. [1] In a mouse model of human ovarian cancer, NMS-E973 produces the antitumor activity by inhibition of Hsp90. [2]

Protocol (from reference)

Kinase Assay:[1]
  • 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.
Animal Study:[1]
  • Animal Models

    Mice bearing A375 xenografts, A2780 xenografts, MOLM-13 xenografts or RKO xenografts.

  • Dosages

    ~60 mg/kg

  • Administration

    i.v.

Customer Product Validation

Data from [Data independently produced by , , Onco Targets Ther, 2018, 11:1583-1593]

Selleck's NMS-E973 has been cited by 9 publications

deepOrganoid: A brightfield cell viability model for screening matrix-embedded organoids [ SLAS Discov, 2022, 27(3):175-184] PubMed: 35314378
HSP90-dependent PUS7 overexpression facilitates the metastasis of colorectal cancer cells by regulating LASP1 abundance [ J Exp Clin Cancer Res, 2021, 40(1):170] PubMed: 33990203
Exosomal circSHKBP1 promotes gastric cancer progression via regulating the miR-582-3p/HUR/VEGF axis and suppressing HSP90 degradation [ Mol Cancer, 2020, 19(1):112] PubMed: 32600329
Febrile Temperature Critically Controls the Differentiation and Pathogenicity of T Helper 17 Cells. [ Immunity, 2020, 52(2):328-341] PubMed: 32049050
Hsp90 inhibitor HSP990 in very low dose upregulates EAAT2 and exerts potent antiepileptic activity [ Theranostics, 2020, 10(18):8415-8429] PubMed: 32724478
Evaluation of [11C]NMS-E973 as a PET tracer for in vivo visualisation of HSP90 [Koen Vermeulen, et al. Theranostics, 2019, 9(2):554-572]
Evaluation of [11C]NMS-E973 as a PET tracer for in vivo visualisation of HSP90. [ Theranostics, 2019, 9(2):554-572] PubMed: 30809293
Hsp90 inhibitor NMS-E973 exerts the anticancer effect against glioblastoma via induction of PUMA-mediated apoptosis. [ Onco Targets Ther, 2018, 11:1583-1593] PubMed: 29593424
Combined inhibition of Hsp90 and heme oxygenase-1 induces apoptosis and endoplasmic reticulum stress in melanoma [Barbagallo I, et al. Acta Histochem, 2015, 117(8):705-11] PubMed: 26493719

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.