SGX-523

SKU: orb1227138

Description

SGX-523 is a potent, selective ATP-competitive inhibitor of MET receptor tyrosine kinase with IC50 of 4 nM, does not inhibit RON and a panel of kinases; shows higher affinity for unphosphorylated form of MET (Ki = 2.7 nM) versus the more active phospho-MET (Ki=23 nM); inhibits MET-mediated signaling, cell proliferation, and cell migration at nanomolar concentrations but has no effect on signaling dependent on other protein kinases; inhibits MET autophosphorylation with IC50 of 40 nM in GTL16 cells, inhibits MET-dependent tumor growth in vivo.Solid Tumors Phase 1 Discontinued(In Vitro):SGX523 shows ATP-competitive inhibition with higher apparent affinity for the less active, unphosphorylated form of MET [MET-KD(0P), Ki=2.7 nM] versus the more active phospho-enzyme [MET-KD(3P), Ki=23 nM].SGX523 inhibits the growth of gastric and lung cancer cell lines with amplification of the MET gene but has no effect, even at high micromolar concentration, on cell lines with normal MET gene copy number. TheIC50s of 0.02, 0.113, and 0.035 μM for NSCLC H1993, gastric cncer MKN45, and gastric cancer Hs746T cells, respectively.The IC50 value for the inhibition of MET autophosphorylation is 0.040 μM in GTL16 cells.SGX523 (0.5, 1.5, 4.6, 13.7, 41, 123, 370, 1100, 3300, 10000 nM; 1 hour) inhibits MET autophosphorylation without affecting total MET or extracellular signal-regulated kinase protein levels in HGF-stimulated A549 cells.(In Vivo):SGX523 exhibits antitumor activity in vivo. SGX523 inhibits MET-dependent tumor growth.

Key Properties

• CAS Number: 1022150-57-7
• MW: 359.4077
• Purity: >98% (HPLC)
• Formula: C₁₈H₁₃N₇S
• SMILES: CN1N=CC(C2=NN3C(C=C2)=NN=C3SC4=CC=C5N=CC=CC5=C4)=C1
• Target: c-Met/HGFR
• Solubility: DMSO: ≥ 3.6 mg/mL

Bioactivity

• In Vivo:
  SGX523 exhibits antitumor activity In vivo. SGX523 inhibits MET-dependent tumor growth. Animal model: Female Harlan nude mice (athymic nu/nu) were s. c. implanted with U87 cells. Dosage: 10 or 30 mg/kg. Administration: Oral gavage; twice daily starting at day 5 for 22 days. Result: Potently inhibited U87MG tumor growth at a dose of 10 mg/kg administered twice daily. Led to clear regression of U87MG tumors at 30 mg/kg dosed twice daily.
• In Vitro:
  SGX523 shows ATP-competitive inhibition with higher apparent affinity for the less active, unphosphorylated form of MET [MET-KD(0P), Ki=2.7 nM] versus the more active phospho-enzyme [MET-KD(3P), Ki=23 nM]. SGX523 inhibits the growth of gastric and lung cancer cell lines with amplification of the MET gene but has no effect, even at high micromolar concentration, on cell lines with normal MET gene copy number. TheIC50s of 0.02, 0.113, and 0.035 μM for NSCLC H1993, gastric cncer MKN45, and gastric cancer Hs746T cells, respectively. The IC50 value for the inhibition of MET autophosphorylation is 0.040 μM in GTL16 cells. SGX523 (0.5, 1.5, 4.6, 13.7, 41, 123, 370, 1100, 3300, 10000 nM; 1 hour) inhibits MET autophosphorylation without affecting total MET or extracellular signal-regulated kinase protein levels in HGF-stimulated A549 cells. Cell Viability Assay Cell line: Gastric cancer cell line GTL16. Concentration: 4.6, 14, 40, 120, 370, 1100, 3300, 10000 nM Incubation time: 1 hours. Result: Abolished constitutive signaling induced by MET gene amplification.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

SGX523 | SGX 523

Quick Database Links

Gene Symbol

c-Met/HGFR