SGX-523

Catalog No.S1112 Batch:S111202

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Technical Data

Formula

C18H13N7S
Molecular Weight 359.41 CAS No. 1022150-57-7
Solubility (25°C)* In vitro DMSO 2 mg/mL (5.56 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.)

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Biological Activity

Description SGX-523 is a selective Met (c-Met) inhibitor with IC50 of 4 nM, no activity to BRAFV599E, c-Raf, Abl and p38α. Phase 1.
Targets
c-Met [1]
(Cell-free assay)
4 nM
In vitro SGX-523 belongs to the class of c-Met/hepatocyte growth factor receptor (HGFR) tyrosine kinase inhibitors. SGX-523 stabilizes MET in a unique inactive conformation that is inaccessible to other protein kinases, suggesting an explanation for its selectivity. SGX523 potently inhibits the purified MET catalytic domain but not the closely related receptor tyrosine kinase RON. SGX523 indicates ATP-competitive inhibition with higher apparent affinity for the less active, unphosphorylated form of MET [MET-KD(0P), with a Ki of 2.7 nM] versus the more active phospho-enzyme [MET-KD(3P), with a Ki of 23 nM], a phenomenon consistent with preferential binding to an inactive enzyme conformation. SGX523 inhibits MET-mediated signaling, cell proliferation and cell migration at nanomolar concentrations but had no effect on signaling dependent on other protein kinases, including the closely related RON, even at micromolar concentrations.[1]
In vivo SGX523 significantly retards the growth of preestablished GTL16 tumors when administered orally at doses of ≥10 mg/kg twice daily. SGX523 potently inhibits U87MG tumor growth; at 30 mg/kg dosed twice daily, SGX523 leads to clear regression of U87MG tumors. SGX523, dosed twice daily at 30 mg/kg, also retards the growth of H441 tumors with concomitant reduction in tumor MET autophosphorylation levels. SGX523 inhibition of MET in vivo is associated with the dose-dependent inhibition of growth of tumor xenografts derived from human glioblastoma, lung and gastric cancers, confirming the dependence of these tumors on MET catalytic activity. [1]

Protocol (from reference)

Kinase Assay:[1]
  • Kinase assays

    Initial rate constants are measured at 21 °C in the presence of 100 mM HEPES (pH 7.5), 0.3 mg/mL poly(Glu-Tyr) peptide substrate, 10 mM MgCl2, 1 mg/mL bovine serum albumin, 5% DMSO, 20 nM MET-KD and various concentrations of ATP and SGX523. Total reaction volumes (20 μL) are quenched with 20 μL Kinase-Glo detection buffer. Luminescence is detected in a plate-reading luminometer and the results are analyzed by nonlinear regression.
Cell Assay:[1]
  • Cell lines

    MDCK cells

  • Concentrations

    200 nM

  • Incubation Time

    18 hours

  • Method

    MDCK cells are seeded at 1 × 103 per well in a 24-well plate and incubated at 37 °C in 5% CO2 for 1 week in MEM and 10% fetal bovine serum. HGF (90 ng/mL) and various concentrations of SGX523 are added and the cells are incubated for another 18 hours (37 °C, 5% CO2 humidified incubator) and visualized. A549 cells are plated in 12-well plates (6 × 104 per well) and incubated to confluence to investigate cell migration. A channel is introduced into the monolayers by scratching with a pipette tip. Various dilutions of compound are added in starve medium in the presence and absence of HGF (90 ng/mL).The wells are checked for cell migration after twenty-fou
Animal Study:[1]
  • Animal Models

    GTL16, U87, or H441 xenografts in Harlan nude mice

  • Dosages

    60 mg/kg

  • Administration

    Oral gavage

Customer Product Validation

Data from [Data independently produced by Biomarkers, 2013, 18(2), 126-35]

Data independently produced by , , Dr. Zhang of Tianjin Medical University

Data from [Data independently produced by , , Sci Rep, 2018, 8(1):1955]

Data from [Data independently produced by , , Acta Pharmacol Sin, 2016, 37(12):1587-1596]

Selleck's SGX-523 has been cited by 135 publications

Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection [ PLoS Pathog, 2023, 19(8):e1011579] PubMed: 37611070
Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection [ PLoS Pathog, 2023, 19(8):e1011579] PubMed: 37611070
Autocrine EGF and TGF-α promote primary and acquired resistance to ALK/c-Met kinase inhibitors in non-small-cell lung cancer [ Pharmacol Res Perspect, 2023, 11(1):e01047] PubMed: 36583451
Candida albicans stimulates the formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection [ bioRxiv, 2023, 2023.02.23.529756] PubMed: 36865306
Selective inhibition of miRNA processing by a herpesvirus-encoded miRNA [ Nature, 2022, 605(7910):539-544] PubMed: 35508655
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
A Ctnnb1 enhancer regulates neocortical neurogenesis by controlling the abundance of intermediate progenitors [ Cell Discov, 2022, 8(1):74] PubMed: 35915089
The transcription factor RFX5 coordinates antigen-presenting function and resistance to nutrient stress in synovial macrophages [ Nat Metab, 2022, 4(6):759-774] PubMed: 35739396
Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies [ Blood, 2022, blood.2021014304] PubMed: 35704690
Anionic nanoplastic exposure induces endothelial leakiness [ Nat Commun, 2022, 13(1):4757] PubMed: 35963861

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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.

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