CP-673451

SKU: orb1225246

Description

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

Key Properties

• CAS Number: 343787-29-1
• MW: 417.5
• Purity: >98% (HPLC)
• Formula: C₂₄H₂₇N₅O₂
• SMILES: NC1CCN(C2=C3N=C(N4C5=CC=C(OCCOC)C=C5N=C4)C=CC3=CC=C2)CC1
• Target: c-Kit
• Solubility: DMSO:28 mg/mL warmed (67.06 mM); Ethanol:4 mg/mL (9.58 mM); Water:<1 mg/mL (<1 mM)

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

CP-673451 | CP673451 | CP 673451 | CP-673,451

Quick Database Links

Gene Symbol

c-Kit

Kristoffer B. Sugg, Michael A. Korn, Dylan C. Sarver, James F. Markworth, Christopher L. Mendias Inhibition of platelet‐derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy FEBS Letters, 591, 801 (2017)

PubMed: 28129672

Applications

In vivo

Reactivity

Mouse