Home Protein Tyrosine Kinase PDGFR inhibitor CP-673451 For research use only.

CP-673451

CP-673451 is a selective inhibitor of PDGFRα/β with IC50 of 10 nM/1 nM in cell-free assays, exhibits >450-fold selectivity over other angiogenic receptors, has antiangiogenic and antitumor activity.

CP-673451 Chemical Structure

CP-673451 Chemical Structure

CAS No. 343787-29-1

Purity & Quality Control

CP-673451 Related Products

Signaling Pathway

PDGFR Signaling Pathways

PDGFR Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
Click to View More Cell Line Experimental Data

Biological Activity

Description CP-673451 is a selective inhibitor of PDGFRα/β with IC50 of 10 nM/1 nM in cell-free assays, exhibits >450-fold selectivity over other angiogenic receptors, has antiangiogenic and antitumor activity.
Targets
PDGFRβ [1]
(Cell-free assay)		 PDGFRα [1]
(Cell-free assay)
1 nM 10 nM
In vitro
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).[1] 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. [2]
Kinase Assay Kinase inhibition assay
A glutathione S-transferase-tagged kinase domain construct of the intracellular portion of the PDGFR-β (amino acids 693-1401, accession no. J03278) is expressed in Sf-9 cells (baculovirus expression system). Enzyme kinetics are determined by incubating the enzyme with increasing concentrations of ATP in phosphorylation buffer [50 mmol/L HEPES (pH 7.3), 125 mmol/L NaCl, 24 mmol/L MgCl2 in Nunc Immuno MaxiSorp 96-well plates previously coated with 100 μL of 100 μg/mL poly-Glu-Tyr (4:1 ratio) diluted in PBS. After 10 minutes, the plates are washed (PBS, 0.1% Tween 20), incubated with anti-phosphotyrosine-horseradish peroxidase antibody, and diluted in PBS, 0.05% Tween 20, 3% BSA for 30 minutes at room temperature. The plates are washed as above and incubated with 3,3
Cell Research Cell lines PAE
Concentrations ~3000 nM
Incubation Time 18 min
Method

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. 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot PDGFR / p-PDGFR / p-AKT / p-BAD / p-S6 / p-P70S6K / P70S6K / p-GSK3β / GSK3β PDGFR / p-PDGFR / p-AKT / p-BAD / p-S6 / p-P70S6K / P70S6K / p-GSK3β / GSK3β 25050066
Growth inhibition assay Cell viability Cell viability 25050066
In Vivo
In vivo

CP 673451 (once-daily p.o. ?0 days dosing routinely) 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 U87MG human glioblastoma multiforme. [1] In RUCH2 xenograft-bearing mice, CP 673451 reduces tumor growth and stromal cell infiltration. [2]
Animal Research Animal Models Athymic female mice
Dosages 3, 10, or 33 mg/kg
Administration Oral gavage

Chemical Information & Solubility

Molecular Weight 417.5 Formula

C24H27N5O2
CAS No. 343787-29-1 SDF Download CP-673451 SDF
Smiles COCCOC1=CC2=C(C=C1)N(C=N2)C3=NC4=C(C=CC=C4N5CCC(CC5)N)C=C3
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 6 mg/mL ( (14.37 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
I need to formulate CP-673451 for animal studies via oral gavage, any suggestions?

Answer:
For oral gavage, S1536 CP-673451 can be dissolved in 30% PEG 400+5% propylene glycol+1% Tween 80+ddH2O at 30 mg/ml as a suspension. When preparing the solution, please add PEG 400 and propylene glycol to the compound first. Sonicate or stir it, then add Tween 80, after they mixed well, then dilute with water.

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