[CAS NO. 343787-29-1] CP-673451
PRODUCTS SPECIFICATIONS [343787-29-1]
DESCRIPTION [343787-29-1]
Overview
| MDL | MFCD11100329 |
|---|---|
| Molecular Weight | 417.50 |
| Molecular Formula | C24H27N5O2 |
| SMILES | NC1CCN(C2=C3N=C(C=CC3=CC=C2)N4C=NC5=CC(OCCOC)=CC=C54)CC1 |
6 Publications Citing Use of MCE
Summary
IC50 & Target
|
PDGFRα 10 nM (IC 50 ) |
PDGFRβ 1 nM (IC 50 ) |
In Vitro
CP-673451 efficiently suppresses the PDGFR downstream signaling pathway. It inhibits phosphorylation of Akt, GSK-3β, p70S6, and S6 in A549 cells in a concentration-dependent manner. CP-673451 (0.0625-4 μM) significantly reduces the viability of NSCLC cell lines A549 and H1299 in a time- and concentration-dependent manner, with IC 50 s of 0.49 and 0.61 μM, respectively. CP-673451 (1, 4 μM) induces apoptosis in non-small-cell lung cancer cells. CP-673451 (25, 100, or 400 nM) is effective at inhibiting migration and invasion of NSCLC cells by suppression of lamellipodia formation [1] . CP-673451 and crenolanib show selective lethality toward cells with CA. U2OS cells treated with 1 to 4 μM CP-673451 or crenolanib show a ruffled cell surface as a sign for alterations of the cortical actin cytoskeleton. CP-673451 attenuates PDGF-BB-induced signaling, and significantly enhances the phosphorylation of PDGFR-β downstream effectors, Akt and MEK [2] . CP-673,451 (0.5 μM) regulates cell proliferation through mechanisms involving reduced phosphorylation of GSK-3α and GSK-3β. CP-673,451 impairs rhabdosphere-forming capacity in both RD and RUCH2 cultures [3] . CP-673,451 inhibits PDGFR-β in PAE-β cells with an IC 50 value of 6.4 nM. Besides, CP-673,451 incubation in H526 and PAE-β cells results in an IC 50 value of 1.1 μM against c-kit [4] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
CP-673451 (20 mg/kg) leads to a medium suppression of tumor growth, while high-dose CP-673451 (40 mg/kg) strongly inhibits tumor growth in mice without significant weitht loss [1] . CP-673,451 (10, 33, and 100 mg/kg, p.o., b.i.d) inhibits the growth of Colo205 tumor in a dose-dependent manner, and similar tumor growth inhibition experiments completes on LS174T, H460, and U87MG xenografts, with no signs of morbidity or weight loss [4] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 100 mg/mL ( 239.52 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.3952 mL | 11.9760 mL | 23.9521 mL |
| 5 mM | 0.4790 mL | 2.3952 mL | 4.7904 mL |
| 10 mM | 0.2395 mL | 1.1976 mL | 2.3952 mL |
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1.
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2.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.75 mg/mL (6.59 mM); Clear solution
References
- [1] Xi Y, et al. CP-673451, a platelet-derived growth-factor receptor inhibitor, suppresses lung cancer cell proliferation and migration. Onco Targets Ther. 2014 Jul 3;7:1215-21.
- [2] Konotop G, et al. Pharmacological Inhibition of Centrosome Clustering by Slingshot-Mediated Cofilin Activation and Actin Cortex Destabilization. Cancer Res. 2016 Nov 15;76(22):6690-6700
- [3] Ehnman M, et al. Distinct effects of ligand-induced PDGFRα and PDGFRβ signaling in the human rhabdomyosarcoma tumor cell and stroma cell compartments. Cancer Res, 2013, 73(7), 2139-2149.
- [4] Roberts WG, et al. Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451. Cancer Res, 2005, 65(3), 957-966.