1. Protein Tyrosine Kinase/RTK
  2. PDGFR

CP-673451 (Synonyms: CP 673451; CP673451)

Cat. No.: HY-12050
Handling Instructions

CP-673451 is a potent selective inhibitor of platelet-derived growth factor receptor (PDGFR), and inhibits PDGFR-α and PDGFR-β kinase with IC50s of 10 and 1 nM, respectively.

For research use only. We do not sell to patients.
CP-673451 Chemical Structure

CP-673451 Chemical Structure

CAS No. : 343787-29-1

Size Price Stock Quantity
Free sample   Apply now  
10 mM * 1 mL in DMSO $150 In-stock
5 mg $136 In-stock
10 mg $256 In-stock
50 mg $776 In-stock
100 mg $1050 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Description

CP-673451 is a potent selective inhibitor of platelet-derived growth factor receptor (PDGFR), and inhibits PDGFR-α and PDGFR-β kinase with IC50s of 10 and 1 nM, respectively.

IC50 & Target

IC50: 10 nM (PDGFR-α), 1 nM (PDGFR-β)[4]

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[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].

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].

References
Preparing Stock Solutions
Concentration Volume (DMSO) 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
Cell Assay
[3]

CP-673451 is dissolved in DMSO and diluted in serum-reduced medium (1.5 % FBS).

Cell proliferation/viability is analyzed using the CyQuant proliferation assay. Pre-starved cells are treated every 24 hours with vehicle (dimethyl sulfoxide) or 0.5 μM CP-673,451 diluted in serum-reduced medium (1.5 % FBS) for 96 hours. The amount of nucleic acid present in lysed cells is normalized to the amount when treatment is initiated. Cell proliferation/viability in response to 300 ng/mL PDGF-CC is likewise analyzed, but cells are then kept in serum-free medium and treated twice during a 48-hour period.

Animal Administration
[1]

CP-673451 is formulated in 10% 1-methyl-2-pyrrolidinone and 90% polyethylene glycol 300.

A subcutaneous A549 xenograft model in nude mice is used to evaluate the anticancer activity of CP-673451. Briefly, A549 cells are injected into the axillary regions of mice (2×106 cells/mouse). When the tumor volumes reach 70 mm3, the mice are randomly assigned to a control group and two CP-673451 groups (n=6 per group): low-dose (20 mg/kg) and high dose (40 mg/kg) groups (vehicle 10% 1-methyl-2-pyrrolidinone and 90% polyethylene glycol 300). These animals are administered intraperitoneally with CP-673451 (20 or 40 mg/kg/day) or with vehicle. During the treatment period, the implanted tumors are measured by caliper once a day in a blind fashion. The animal body weights are also measured at the same time. The tumor volume is calculated as follows: (width × width × length)/2. After treatment, the mice are killed, and the tumors are harvested and analyzed.

References
M.Wt

417.5

Formula

C₂₄H₂₇N₅O₂

CAS No.

343787-29-1

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

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Product Name:
CP-673451
Cat. No.:
HY-12050
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