NT157

Catalog No.S8228

NT157 Chemical Structure

Molecular Weight(MW): 412.26

NT157, a selective inhibitor of IRS-1/2(insulin receptor substrate), has the potential to inhibit IGF-1R and STAT3 signaling pathways in cancer cells and stroma cells of TME leading to a decrease in cancer cell survival.

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Biological Activity

Description NT157, a selective inhibitor of IRS-1/2(insulin receptor substrate), has the potential to inhibit IGF-1R and STAT3 signaling pathways in cancer cells and stroma cells of TME leading to a decrease in cancer cell survival.
Targets
IRS1/2 [2]
In vitro

NT157 treatment resulted in dose-dependent inhibition of IGF1R activation, suppression of IRS protein expression, inhibition of IGF1-induced AKT activation, but increased ERK activation in NT157-treated cells in vitro. These effects were correlated with decreased proliferation and increasing apoptosis of LNCaP cells and increasing G2-M arrest in PC3 cells. NT157 can mediate suppression of IGF1R-mediated survival signaling through the established mechanism for negative feedback of IGF1R signaling: targeting IRS1/2 for serine phosphorylation and subsequent degradation[1]. NT157 displayed little to no effect on the survival of normal melanocytes and fibroblasts[2].

Assay
Methods Test Index PMID
Western blot
IRS-1 / IRS-2 ; 

PubMed: 26029165     


Inhibition of cell motility is mediated by downregulation of IRS-2 and IRS-1 in MG-63 and U-2OS cells after 24 h of treatment with NT157 (1–3 μM). β-actin was used as loading control.

p-IRS1 / p-AKT / AKT / p-S6 / S6 / Shc / p-ERK / ERK ; 

PubMed: 26029165     


Analysis of major downstream signaling of IRS-1 after treatment with or without NT157 (1-3 μM) by western blotting using 40 μg of total protein cell lysate. GAPDH was used as a loading control. The figure shows data representative of two independent experiments.

26029165
Growth inhibition assay
Cell viability; 

PubMed: 26029165     


The in vitro sensitivity to a selected inhibitor of IRS-1/2, NT157, for a panel of OS cell lines. Cell growth was assessed by staining cells with Trypan Blue and counting viable cells after up to 72 h of exposure to NT157 (0.3-3 μM) in MG-63, OS-19, and U-2OS cells. Points indicate three independent experiments; barsindicate the SE.

26029165
In vivo NT157 suppressed androgen-responsive growth, delayed CRPC progression of LNCaP xenografts, and suppressed PC3 tumor growth alone and in combination with docetaxel[1]. Melanoma tumor growth and metastasis is efficiently inhibited by NT157[2].

Protocol

Cell Research:[1]
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  • Cell lines: LNCaP cells, PC3 cells
  • Concentrations: 0-10 μM
  • Incubation Time: 72 h
  • Method: Cells were plated in 24-well plates and treated with varying doses of NT157. Crystal violet staining was carried out for time course, and 72 hours after treatment. The absorbance was determined with a microtiter plate reader at 562 nm. Cell survival after NT157 treatment was calculated as the percentage of the absorbance in vehicle-treated cells.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: Athymic nude mice (Harlan Sprague-Dawley)
  • Formulation: 20% 2-hydroxypropyl-β-cyclodextrin, 0.67% NaCl/H2O
  • Dosages: 50 mg/kg
  • Administration: i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 82 mg/mL (198.9 mM)
Ethanol 82 mg/mL (198.9 mM)
Water 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.

Chemical Information

Molecular Weight 412.26
Formula

C16H14BrNO5S

CAS No. 1384426-12-3
Storage powder
in solvent
Synonyms N/A

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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IGF-1R Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID