CP-673451
CP-673451 is a potent inhibitor of PDGFR with IC50 value of 10nM and 1nM for PDGFR-α and PDGFR-β, respectively [1].
CP-673451 is an ATP-competitive inhibitor and is investigated to treat for cancer. It is highly selective against PDGFR-α and PDGFR-β over a variety of other kinases such as VEGFR-1, VEGFR-2, Lck, TIE-2 and EGFR. In PAE-β cells, CP-673451 inhibits PDGFR-β with IC50 value of 6.4nM. CP-673451 also inhibits c-kit with IC50 value of 1.1μM in H526 cells. In rat C6 glioblastoma xenograft models, a single oral dose of 50mg/kg CP-673451 reduces > 50% phosphorylation of PDGFR-β for 4 hours. In addition, CP-673451 is found to inhibit PDGF-BB-induced angiogenesis in a sponge angiogenesis model. Furthermore, CP-673451 inhibits the tumor growth in Colo205, LS174T, H460, and U87MG xenograft models. It also reduces the microvessel density of Colo205 xenografts [1].
References:
[1] Roberts W G, Whalen P M, Soderstrom E, et al. Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451. Cancer research, 2005, 65(3): 957-966.
| Storage | Store at -20°C |
| M.Wt | 417.52 |
| Cas No. | 343787-29-1 |
| Formula | C24H27N5O2 |
| Solubility | insoluble in H2O; ≥2.39 mg/mL in EtOH with gentle warming and ultrasonic; ≥20.9 mg/mL in DMSO |
| Chemical Name | 1-[2-[5-(2-methoxyethoxy)benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine |
| SDF | Download SDF |
| Canonical SMILES | COCCOC1=CC2=C(C=C1)N(C=N2)C3=NC4=C(C=CC=C4N5CCC(CC5)N)C=C3 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
PAE-β cells and H526 cells |
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Preparation method |
The solubility of this compound in DMSO is > 20.9 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0 nM ~ 3 mM |
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Applications |
In PAE-β cells, CP-673451 inhibited PDGFR-β in a dose-dependent manner, with the IC50 value of 6.4nM. CP-673451 also inhibited c-kit in H526 cells, with the IC50 value of 1.1 μM. However, CP-673451 was > 180× selective for PDGFR-β compared with c-kit in H526 cells. |
| Animal experiment [1]: | |
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Animal models |
Mouse sponge angiogenesis model |
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Dosage form |
3, 10 or 30 mg/kg; p.o.; q.d., for 5 days |
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Applications |
CP-673451 (3, 10 or 30 mg/kg; p.o.; q.d., for 5 days) inhibited PDGF-BB-induced angiogenesis by 70 ~ 90%. Corresponding Cmax plasma concentrations after the last dose were 5.5 ~ 419 ng/mL. Besides, CP-673451 showed selective inhibition on PDGF-BB-induced angiogenesis over VEGF- or bFGF-induced angiogenesis (no inhibition observed). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Roberts W G, Whalen P M, Soderstrom E, et al. Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451. Cancer research, 2005, 65(3): 957-966. | |
| Description | CP-673451 is a selective inhibitor of PDGFRα/β with IC50 values of 10 nM/1 nM,respectively. | |||||
| Targets | PDGFRβ | PDGFRα | c-Kit | VEGFR1 | VEGFR2 | |
| IC50 | 1 nM | 10 nM | 252 nM | 450 nM | 450 nM | |
Quality Control & MSDS
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Chemical structure
