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Chemical Structure| 343787-29-1 Chemical Structure| 343787-29-1

Structure of CP-673451
CAS No.: 343787-29-1

Chemical Structure| 343787-29-1

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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.

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Product Details of CP-673451

CAS No. :343787-29-1
Formula : C24H27N5O2
M.W : 417.50
SMILES Code : NC1CCN(C2=C3N=C(N4C=NC5=CC(OCCOC)=CC=C45)C=CC3=CC=C2)CC1
MDL No. :MFCD11100329
InChI Key :DEEOXSOLTLIWMG-UHFFFAOYSA-N
Pubchem ID :10158940

Safety of CP-673451

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of CP-673451

RTK

Isoform Comparison

Biological Activity

Target
  • PDGFRβ

    PDGFRβ, IC50:1 nM

  • PDGFRα

    PDGFRα, IC50:10 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
Human placental pericytes 0.01–100 µM 24 hours To measure the direct effects of sunitinib on pericyte viability, showing a dose-dependent impairment of pericyte viability. PMC3833098
Ba/F3 cells 9.448 nM 72 hours To evaluate the inhibitory effect of CP-673451 on the MYH9::PDGFRB fusion gene, results showed that Ba/F3 cells were highly sensitive to CP-673451 PMC11063843
CTV-1 cells 230 nM 72 hours To evaluate the inhibitory effect of CP-673451 on CTV-1 cells, results showed that CTV-1 cells were sensitive to CP-673451 PMC11063843
T-ALL1 PDX cells <5 nM 72 hours To evaluate the inhibitory effect of CP-673451 on T-ALL1 PDX cells, results showed that T-ALL1 PDX cells were highly sensitive to CP-673451 PMC11063843
Pten−/−MEFs 2 μM 24 hours To evaluate the effect of MK-2206 on PDGFRα expression in Pten−/−MEFs. Results showed that MK-2206 significantly inhibited PDGFRα expression. PMC7876135
U373 cells 5 μM 24 hours To evaluate the effect of MK-2206 on PDGFRα expression in U373 cells. Results showed that MK-2206 significantly inhibited PDGFRα expression. PMC7876135
RAW264.7 macrophages 20 μg/mL 8, 16, 24 hours To investigate the effect of CP-673451 on the transcription levels of CCL1, CCL2, CCL7, CXCL11, IL-1β, IL-6, IL-10, and TNF-α in LPS-stimulated RAW264.7 macrophages, results showed that CP-673451 significantly reduced the transcription levels of CCL2, CCL7, IL-10, and TNF-α. PMC6841710
Human brain vascular pericytes 10 ng/mL 4 hours To evaluate the effect of TGF-β on the expression of pSMAD3 and KLF4 in HBVPs, results showed that TGF-β significantly increased the expression of pSMAD3 and KLF4. PMC9713377
U87 GBM cells 1 μM 24 hours triggers outgrowth of neurite-like processes, suggesting differentiation into neural-like cells PMC9076540
G166 GSCs 1 μM 48 hours significantly increased the average neurite-like process length, indicating differentiation PMC9076540
GS090 GSCs 1 μM 48 hours significantly increased the average neurite-like process length, indicating differentiation PMC9076540
G179 GSCs 1 μM 48 hours significantly increased the average neurite-like process length, indicating differentiation PMC9076540
bovine embryonic cells 100 nM 3 days To investigate the inhibitory effect of CP-673451 on PDGFR and its impact on NFYA expression and bovine embryonic development. Results showed that CP-673451 significantly reduced NFYA expression and nuclear localization, and decreased the developmental rate of bovine embryos. PMC10707662

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Sprague–Dawley (SD) rats sepsis model gastric gavage 100 mg/kg Single dose CP-673451 was used to selectively inhibit PDGFR-β. After 7 consecutive days of administration, it successfully reduced the amount of vascular pericytes within the rat mesentery and decreased the expression of pericyte markers (NG-2 and PDGFR-β) in mesenteric microvascular networks. PMC10010010
Mice Oral gavage 75 mg/kg/day Once daily for 14 days To evaluate the effects of CP-673451 on cardiac function in mice, showing a decrease in ejection fraction and coronary flow reserve, similar to the effect seen with sunitinib. PMC3833098
NSG-SGM3 mice T-ALL patient-derived xenograft model intraperitoneal injection 10 mg/kg once daily for 10 weeks To evaluate the therapeutic effect of CP-673451 on the T-ALL1 PDX model, results showed that CP-673451 significantly delayed leukemia progression PMC11063843
Nude mice U373 cell subcutaneous xenograft model Intraperitoneal injection ceritinib (30 mg/kg), AZD1208 (15 mg/kg) daily for 14 days To evaluate the therapeutic efficacy of MK-2206 and CP-673451 alone or in combination on U373 cell subcutaneous xenografts. Results showed that the combination of MK-2206 and CP-673451 significantly inhibited tumor growth. PMC7876135
mice cecal ligation puncture (CLP) model gavage 10 mg/kg 3 times a week for 2 weeks To investigate the effect of CP-673451 on the survival rate of CLP model mice, results showed that CP-673451 significantly decreased the mortality of CLP mice. PMC9345782
Mice Ccm1ECKO mice Intraperitoneal injection 200 mg/kg administered at 2, 24, 48, and 72h after CLP To evaluate the effect of CP-673451 on pericyte function in Ccm1ECKO mice, results showed that CP-673451 significantly downregulated PDGFRβ expression and exacerbated CCM lesion development. PMC9713377
mice U87 GBM cell subcutaneous xenograft model oral 30 or 60 mg/kg Every 12 hours for 2 days, repeated weekly for 4 weeks CP-673451 treatment significantly improved the anti-tumour effects of temozolomide PMC9076540
Sprague-Dawley (SD) rats Sepsis model Gastric gavage 40 mg/(kg·d) 7 consecutive days Depletion of pericytes using CP-673451, a selective PDGFR-β inhibitor, to study its role in sepsis. PMC10010010

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.40mL

0.48mL

0.24mL

11.98mL

2.40mL

1.20mL

23.95mL

4.79mL

2.40mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2
 

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