PD-166866

SKU: orb1304150

Description

PD-166866 is a potent and selective small-molecule inhibitor of fibroblast growth factor receptor (FGFR) tyrosine kinase. It is utilized in oncology research to study FGFR-driven signaling pathways in both cellular assays and animal models, aiding the investigation of tumor proliferation and angiogenesis.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 192705-79-6
• MW: 396.44
• Purity: 98.29%
• Formula: C₂₀H₂₄N₆O₃
• SMILES: COc1cc(OC)cc(c1)-c1cc2cnc(N)nc2nc1NC(=O)NC(C)(C)C
• Target: Autophagy,FGFR
• Solubility: Ethanol:3 mg/mL (7.57 mM);DMSO:12 mg/mL (30.27 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  FGFR1:52.4 nM
• In Vitro:
  The treatment with PD166866 apparently causes a mitochondrial deficit and an oxidative stress. PD 166866 inhibits human full-length FGFR-1 tyrosine kinase with an IC50 value of 52.4 ± 0.1 nM but has no effect on c-Src, platelet-derived growth factor receptor-β, epidermal growth factor receptor or insulin receptor tyrosine kinases or on mitogen-activated protein kinase, protein kinase C and CDK4 at concentrations as high as 50 μM. PD 166866 is a potent inhibitor of basic fibroblast growth factor (bFGF)-mediated receptor autophosphorylation in NIH 3T3 cells expressing endogenous FGFR-1 and in L6 cells overexpressing the human FGFR-1 tyrosine kinase, confirming a tyrosine kinase-mediated mechanism. PD 166866 does not inhibit platelet-derived growth factor, epidermal growth factor or insulin-stimulated receptor autophosphorylation in vascular smooth muscle, A431 or NIHIR cells, respectively, further supporting its specificity for the FGFR-1. Besides, PD 166866 is found to be a potent inhibitor of microvessel outgrowth (angiogenesis) from cultured artery fragments of human placenta. Phosphorylated 44- and 42-kDa MAPK isoforms are inhibited in L6 cells by PD 166866 with IC50 values of 4.3 and 7.9 nM, respectively. PD166866 induces autophagy through repressing Akt/mTOR signaling pathway.
• Cell Research:
  HeLa cells are treated with PD166866 for 24 hours, the growth medium is removed, the cells are washed with PBS and fixed for 1 hour at 25°C adding a freshly made paraformaldheyde solution (4% in PBS). Samples are washed again with PBS and the endogenous oxidases were blocked for 2 minutes in the dark. Further washes with PBS followed and blocking the unspecific sites is done for 1 hour at 25℃. PARP is evidenced by immunolocalization utilizing a polyclonal antibody, directed against the N-terminal proteolytic fragment. Immuno-reaction is revealed by a secondary anti-rabbit antibody after incubation for 16 hours at 4°C. After exhaustive washing with PBS the samples are incubated for 30 minutes in solution ABC. Eventually, DAB (3,3'-Diaminobenzidine) is added and the samples are incubated for 10 minutes in the dark. The samples are washed again the plates are sealed and ready for microscopic observation.(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

Autophagy, PD 166866, PD166866, PD-166866, inhibit, Inhibitor, FGFR1, FGFR, Fibroblast growth factor receptor

Compound Identifiers

PubChem CID

5328127