S49076

SKU: orb1304357

Description

S49076 is a novel small molecule inhibitor targeting receptor tyrosine kinases MET, AXL/MER, and FGFR1/2/3. It effectively blocks their cellular phosphorylation and has demonstrated activity in preclinical in vitro and in vivo cancer models, supporting its use in oncology research.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1265965-22-7
• MW: 438.5
• Purity: 97.40% (May vary between batches)
• Formula: C₂₂H₂₂N₄O₄S
• SMILES: O=C1CSC(=O)N1Cc1ccc2NC(=O)\C(=C/c3cc(CN4CCOCC4)c[nH]3)c2c1
• Target: TAM Receptor,FGFR,c-Met/HGFR
• Solubility: DMSO:81 mg/mL (184.72 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (7.53 mM)

Bioactivity

• Target IC50:
  MET:1 nM|FGFR2:17 nM|Axl:7 nM|Mer:2 nM|FGFR2 (N549H):19 nM|FGFR1:18 nM|FGFR3:15 nM|FGFR1 V561M:23 nM
• In Vivo:
  S49076 shows marked antitumor activity in MET- and FGFR-dependent tumor xenografts at well-tolerated doses. S49076 has high distribution to tumors, in which the half-life for the dose of 3.125 mg/kg is approximately 7 hours versus less than 2 hours in the blood. At doses of 6.25 mg/kg and higher, more than 50% inhibition of MET phosphorylation is retained at 16 hours. S49076 is also active in a bevacizumab-resistant model and totally inhibits the growth of colon carcinoma xenografts in association with bevacizumab.
• In Vitro:
  S49076 potently blocks cellular phosphorylation of MET, AXL, and FGFRs, inhibiting downstream signaling both in vitro and in vivo. In cell models, S49076 inhibits proliferation of MET- and FGFR2-dependent gastric cancer cells, blocks MET-driven lung carcinoma cell migration, and inhibits colony formation of hepatocarcinoma cells expressing FGFR1/2 and AXL. S49076 also inhibits viability, motility, and three-dimensional colony formation of cancer cells expressing MET, AXL, or FGFRs.
• Cell Research:
  For GTL-16 and SNU-16 viability assays, cells are seeded in 96-well microplates at the appropriate density in media containing 10% FCS and supplemented 48 hours later with serial dilutions of S49076 in a final volume of 150 μL per well. After 96 hours (GTL-16) or 120 hours (SNU-16) incubation, 15 μL of a solution of 5 mg/mL MTT is added to each well and the plates are incubated for 4 hours at 37℃. The formazan metabolite is solubilized in SDS for SNU-16 and, following removal of the MTT solution, in DMSO for GTL-16. Global cell viability is estimated by measurement of optical density at 540 nm. (Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, Mer, Met, Fibroblast growth factor receptor, FGFR, FGFR3, FGFR2, Inhibitor, HGFR, c-Met/HGFR, c-Met, cMet/HGFR, cMet, AXL, S49076, S-49076, S 49076, TAMReceptor, TAM Receptor

Compound Identifiers

PubChem CID

49870909