PF-04217903

SKU: orb1305179

Description

PF-04217903 is an orally bioavailable, small-molecule inhibitor targeting the MET tyrosine kinase, exhibiting antineoplastic potential. It has been utilized in preclinical research to investigate MET-driven oncogenesis, demonstrating activity in both in vitro cellular assays and in vivo tumor models.

Research Area

Signal Transduction

Key Properties

• CAS Number: 956905-27-4
• MW: 372.38
• Purity: 98.55% (May vary between batches)
• Formula: C₁₉H₁₆N₈O
• SMILES: OCCn1cc(cn1)-c1cnc2nnn(Cc3ccc4ncccc4c3)c2n1
• Target: c-Met/HGFR
• Solubility: DMSO:20 mg/mL (53.71 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+90% Corn Oil:2 mg/mL (5.37 mM)

Bioactivity

• Target IC50:
  c-Met:4.8 nM
• In Vivo:
  PF-04217903 markedly inhibits the clonal growth of LXFA 526L and LXFA 1647L, with IC50 values of 16 nM and 13 nM, respectively, and its efficacy is enhanced when used in combination with cetuximab. It effectively inhibits c-Met-driven biological processes, including the growth, movement, invasion, and morphological changes of various tumor cells. At a concentration of 2 μM, PF-04217903 promotes cell death in GTL-16 cells, involving the downregulation of phosphorylated 4E-BP1, ERK/MAPK-related proteins, and the PI3K/AKT pathway. PF-04217903 exhibits higher selectivity compared to crizotinib or PF-02341066, with over 1000 times greater selectivity for c-Met than for a panel of 208 other kinases, and it is more sensitive to c-Met oncogenic mutations. Besides WT c-Met, PF-04217903 similarly inhibits the activity of c-Met-H1094R, c-Met-R988C, and c-Met-T1010I mutants with IC50 values of 3.1 nM, 6.4 nM, and 6.7 nM, respectively, but it does not inhibit c-Met-Y1230C with an IC50 of >10 μM. Combined with sunitinib, PF-04217903 significantly inhibits endothelial cell proliferation without affecting tumor cells such as B16F1, Tib6, EL4, and LLC.
• In Vitro:
  Although PF-04217903 and sunitinib combination therapy does not inhibit tumor growth in sunitinib-sensitive B16F1 and Tib6 tumor models, it significantly inhibits tumor growth and angiogenesis in sunitinib-resistant EL4 and LLC tumor models compared to the administration of either sunitinib or PF-04217903 alone. This indicates the functional role of the HGF/c-Met axis in sunitinib-resistant tumors.
• Cell Research:
  Cells are treated with different concentrations PF-04217903 for 4 days. Cell proliferation is assessed by counting content of each well using a Coulter counter machine.(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

phosphorylation, phospho-PDGFRβ, PF 04217903, PF04217903, PF-04217903, colon, c-Met/HGFR, c-Met, cMet/HGFR, cMet, carcinoma, inhibit, migration, lung, Inhibitor, HGFR, gastric, GTL-16

Compound Identifiers

PubChem CID

17754438