CP-673451 is a potent and selective inhibitor of PDGFR with IC50s of 10 and 1 nM for PDGFRα and PDGFRβ, respectively.
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 IC50s 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 IC50 value of 6.4 nM. Besides, CP-673,451 incubation in H526 and PAE-β cells results in an IC50 value of 1.1 μM against c-kit[4].
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].
| Catalog Number | I003251 |
| CAS Number | 343787-29-1 |
| Synonyms | 1-[2-[5-(2-methoxyethoxy)benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine |
| Molecular Formula | C24H27N5O2 |
| Purity | % |
| InChI | InChI=1S/C24H27N5O2/c1-30-13-14-31-19-6-7-21-20(15-19)26-16-29(21)23-8-5-17-3-2-4-22(24(17)27-23)28-11-9-18(25)10-12-28/h2-8,15-16,18H,9-14,25H2,1H3 |
| InChIKey | DEEOXSOLTLIWMG-UHFFFAOYSA-N |
| SMILES | COCCOC1=CC2=C(C=C1)N(C=N2)C3=NC4=C(C=CC=C4N5CCC(CC5)N)C=C3 |
| Reference | [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. |
