CP-673451

SKU: orb1301081

Description

CP-673451 is a potent and selective PDGFRα/β inhibitor (IC50: 10/1 nM) with demonstrated antiangiogenic and antitumor activity in research models. It exhibits over 450-fold selectivity against related kinases. This compound is utilized in vitro and in vivo to study PDGF signaling in cancer, fibrosis, and cardiovascular disease research.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 343787-29-1
• MW: 417.5
• Purity: 99.93%
• Formula: C₂₄H₂₇N₅O₂
• SMILES: COCCOc1ccc2n(cnc2c1)-c1ccc2cccc(N3CCC(N)CC3)c2n1
• Target: PDGFR,c-Kit,VEGFR
• Solubility: Ethanol:41.8 mg/mL (100.12 mM);DMSO:20.83 mg/mL (49.89 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.79 mM)

Bioactivity

• Target IC50:
  PDGFRα:10 nM|PDGFRβ:1 nM
• In Vivo:
  CP 673451 (once-daily p.o.) inhibits tumor growth (ED50 < 33 mg/kg) in a number of human tumor xenografts grown s.c. in athymic mice, including H460 human lung carcinoma, Colo205 and LS174T human colon carcinomas, and U87 mg human glioblastoma multiforme. In RUCH2 xenograft-bearing mice, CP 673451 reduces tumor growth and stromal cell infiltration.
• In Vitro:
  CP 673451 is a selective inhibitor of PDGFRα/β with IC50 of 10 nM/1 nM, exhibits >450-fold selectivity over other angiogenic receptors. In glioblastoma tumors, CP-673451 (33 mg/kg) provides >50% inhibition of PDGFR-β receptor for 4 hours corresponding to an EC50 of 120 ng/mL in plasma at Cmax. In a sponge angiogenesis model, CP-673451 inhibits 70% of PDGF-BB-stimulated angiogenesis at a dose of 3 mg/kg (q.d. ×5, p.o., corresponding to 5.5 ng/mL at Cmax). CP-673451 decreases cell proliferation rate through mechanisms involving reduced phosphorylation of GSK-3α and GSK-3β. In both RD and RUCH2 cultures, CP-673451 impairs rhabdosphere-forming capacity and cell differentiation, causes increased senescence.
• Cell Research:
  PAE cells stably expressing full-length PDGFR and VEGFR have been generated. For cell-based selectivity assays, PAE cells are transfected with fulllength human PDGFR-a, PDGFR-h, or VEGFR-2. Cells are seeded at 4×105 cells/mL in 50 μL growth medium (Ham's F-12 media supplemented with 10% fetal bovine serum, 50,000 units each penicillin and streptomycin, and 500 μg/mL gentamicin) per well in 96-well plates. After 6 to 8 hours, the growth medium is replaced with 50 μL serum-depleted medium (as above, but with 0.1% fetal bovine serum) and cells are incubated overnight. Immediately before compound addition, the medium was replaced with 95 μL serum-depleted medium. Compounds are diluted in 100% DMSO, added to the cells at a final DMSO concentration of 0.25% v/v, and incubated at 37°C for 10 minutes. Cells are stimulated with the appropriate ligand and incubated as above for an additional 8 minutes. The medium is removed and the cells washed once with PBS, then lysed with 50 μL HNTG buffer [20 mmol/L HEPES (pH 7.5), 150 mmol/L NaCl, 2% Triton X-100, 10% glycerol, 5 μmol/L EDTA, 2 mmol/L NaVO4, and 1 EDTA-free complete protease inhibitor tablet per 25 mL] for 5 minutes at room temperature. Lysates are then diluted with 50 μL HG buffer [20 mmol/L HEPES (pH 7.5), 10% glycerol]. The diluted cell lysates are mixed thoroughly, 50 μL of supernatant are transferred to the ELISA capture plate, and incubated at room temperature for 2 hours with agitation. ELISA capture plates are prepared by coating 96-well ReactiBind goat-antirabbit plates with 100 μL/well of 5 μg/mL rabbit anti-human PDGFR-h, anti-PDGFR-a, or anti-VEGFR-2 antibody for 60 to 90 minutes. At the end of the 2-hour incubation the plates are washed (PBS, 0.1% Tween 20) before incubation with anti-phosphotyrosine-horseradish peroxidase antibody (diluted in PBS, 0.05% Tween 20) for 30 minutes at room temperature. The plates are washed again, then incubated with tetramethylbenzidine and evaluated as described above.IC50 values are calculated as percent inhibition of control.(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

CP673451, CP-673451, CP 673451, cKit, c-Kit, inhibit, Inhibitor, Platelet-derived growth factor receptor, PDGFR, PDGFRβ, PDGFRα, VEGFR1, VEGFR2

Compound Identifiers

PubChem CID

10158940