CP-673451

製品コードS1536 バッチS153602

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₄H₂₇N₅O₂
	分子量	417.5	CAS No.	343787-29-1
Solubility (25°C)*	体外	DMSO	84 mg/mL warmed with 50ºC water bath (201.19 mM)
		Ethanol	60 mg/mL (143.71 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	CP-673451 is a selective inhibitor of PDGFRα/β with IC50 of 10 nM/1 nM in cell-free assays, exhibits >450-fold selectivity over other angiogenic receptors, has antiangiogenic and antitumor activity.
in vitro	CP 673451 is a selective inhibitor of PDGFRα/β with IC50 of 10 nM/1 nM, exhibits >450-fold selectivity over other angiogenic receptors. In glioblastoma tumors, CP-673451 (33 mg/kg) provides >50% inhibition of PDGFR-β receptor for 4 hours corresponding to an EC50 of 120 ng/mL in plasma at C_max. In a sponge angiogenesis model, CP-673451 inhibits 70% of PDGF-BB-stimulated angiogenesis at a dose of 3 mg/kg (q.d. ×5, p.o., corresponding to 5.5 ng/mL at C_max).^[1] CP-673451 decreases cell proliferation rate through mechanisms involving reduced phosphorylation of GSK-3α and GSK-3β. In both RD and RUCH2 cultures, CP-673451 impairs rhabdosphere-forming capacity and cell differentiation, causes increased senescence. ^[2]
in vivo	CP 673451 (once-daily p.o. ?0 days dosing routinely) inhibits tumor growth (ED50 < 33 mg/kg) in a number of human tumor xenografts grown s.c. in athymic mice, including H460 human lung carcinoma, Colo205 and LS174T human colon carcinomas, and U87MG human glioblastoma multiforme. ^[1] In RUCH2 xenograft-bearing mice, CP 673451 reduces tumor growth and stromal cell infiltration. ^[2]

プロトコル(参考用のみ)

キナーゼアッセイ	Kinase inhibition assay
キナーゼアッセイ	A glutathione S-transferase-tagged kinase domain construct of the intracellular portion of the PDGFR-β (amino acids 693-1401, accession no. J03278) is expressed in Sf-9 cells (baculovirus expression system). Enzyme kinetics are determined by incubating the enzyme with increasing concentrations of ATP in phosphorylation buffer [50 mmol/L HEPES (pH 7.3), 125 mmol/L NaCl, 24 mmol/L MgCl₂ in Nunc Immuno MaxiSorp 96-well plates previously coated with 100 μL of 100 μg/mL poly-Glu-Tyr (4:1 ratio) diluted in PBS. After 10 minutes, the plates are washed (PBS, 0.1% Tween 20), incubated with anti-phosphotyrosine-horseradish peroxidase antibody, and diluted in PBS, 0.05% Tween 20, 3% BSA for 30 minutes at room temperature. The plates are washed as above and incubated with 3,3',5,5'-tetramethylbenzidine. The reaction is stopped by adding an equal volume of 0.09 NaH₂SO₄. The phosphotyrosine-dependent signal is then quantitated on a plate reader at 450 nm. For routine enzyme assays, the enzyme is incubated with 10 μM ( final) ATP in the presence of compound diluted in DMSO (1.6% v/v DMSO assay final) for 30 minutes at room temperature in plates, as above, previously coated with 100 μL of 6.25 μg/mL poly-Glu-Tyr. The remainder of the assay is carried out as above, and IC50 values are calculated as percent inhibition of control.
細胞アッセイ	細胞株	PAE
	濃度	~3000 nM
	反応時間	18 min
	実験の流れ	PAE cells stably expressing full-length PDGFR and VEGFR have been generated. For cell-based selectivity assays, PAE cells are transfected with fulllength human PDGFR-a, PDGFR-h, or VEGFR-2. Cells are seeded at 4×10⁵ cells/mL in 50 μL growth medium (Ham's F-12 media supplemented with 10% fetal bovine serum, 50,000 units each penicillin and streptomycin, and 500 μg/mL gentamicin) per well in 96-well plates. After 6 to 8 hours, the growth medium is replaced with 50 μL serum-depleted medium (as above, but with 0.1% fetal bovine serum) and cells are incubated overnight. Immediately before compound addition, the medium was replaced with 95 μL serum-depleted medium. Compounds are diluted in 100% DMSO, added to the cells at a final DMSO concentration of 0.25% v/v, and incubated at 37°C for 10 minutes. Cells are stimulated with the appropriate ligand and incubated as above for an additional 8 minutes. The medium is removed and the cells washed once with PBS, then lysed with 50 μL HNTG buffer [20 mmol/L HEPES (pH 7.5), 150 mmol/L NaCl, 2% Triton X-100, 10% glycerol, 5 μmol/L EDTA, 2 mmol/L NaVO₄, and 1 EDTA-free complete protease inhibitor tablet per 25 mL] for 5 minutes at room temperature. Lysates are then diluted with 50 μL HG buffer [20 mmol/L HEPES (pH 7.5), 10% glycerol]. The diluted cell lysates are mixed thoroughly, 50 μL of supernatant are transferred to the ELISA capture plate, and incubated at room temperature for 2 hours with agitation. ELISA capture plates are prepared by coating 96-well ReactiBind goat-antirabbit plates with 100 μL/well of 5 μg/mL rabbit anti-human PDGFR-h, anti-PDGFR-a, or anti-VEGFR-2 antibody for 60 to 90 minutes. At the end of the 2-hour incubation the plates are washed (PBS, 0.1% Tween 20) before incubation with anti-phosphotyrosine-horseradish peroxidase antibody (diluted in PBS, 0.05% Tween 20) for 30 minutes at room temperature. The plates are washed again, then incubated with tetramethylbenzidine and evaluated as described above. IC50 values are calculated as percent inhibition of control.
動物実験	動物モデル	Athymic female mice
	投薬量	3, 10, or 33 mg/kg
	投与方法	Oral gavage

参考

カスタマーフィードバック

: Data from [Data independently produced by Stem Cells, 2014, 10.1002/stem.1865]

: Data from [Data independently produced by Onco Targets Ther, 2014, 7, 1215-21]

: Data from [Data independently produced by , , Environ Toxicol Pharmacol, 2016, 46:168-73.]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function: implication of miRNAs and microvesicles [ Mil Med Res, 2023, 10(1):13]	PubMed: 36907884
CP-673451, a Selective Platelet-Derived Growth Factor Receptor Tyrosine Kinase Inhibitor, Induces Apoptosis in Opisthorchis viverrini-Associated Cholangiocarcinoma via Nrf2 Suppression and Enhanced ROS [ Pharmaceuticals (Basel), 2023, 17(1)9]	PubMed: 38275995
MiR-3529-3p from PDGF-BB-induced cancer-associated fibroblast-derived exosomes promotes the malignancy of oral squamous cell carcinoma [ Discov Oncol, 2023, 14(1):166]	PubMed: 37668846
MiR-3529-3p from PDGF-BB-induced cancer-associated fibroblast-derived exosomes promotes the malignancy of oral squamous cell carcinoma [ Discov Oncol, 2023, 14(1):166]	PubMed: 37668846
Microglia-derived PDGFB promotes neuronal potassium currents to suppress basal sympathetic tonicity and limit hypertension [ Immunity, 2022, S1074-7613(22)00291-6]	PubMed: 35863346
Recapitulating early human development with 8C-like cells [ Cell Rep, 2022, 39(12):110994]	PubMed: 35732112
AKT1-CREB stimulation of PDGFRα expression is pivotal for PTEN deficient tumor development [ Cell Death Dis, 2021, 12(2):172]	PubMed: 33568640
Patient-derived xenografts and in vitro model show rationale for imatinib mesylate repurposing in HEY1-NCoA2-driven mesenchymal chondrosarcoma [ Lab Invest, 2021, 10.1038/s41374-021-00704-4]	PubMed: 34837064
Platelet‑derived growth factor‑BB mediates pancreatic cancer malignancy via regulation of the Hippo/Yes‑associated protein signaling pathway [ Oncol Rep, 2021, 45(1):83-94]	PubMed: 33416116
PDGF-BB regulates the transformation of fibroblasts into cancer-associated fibroblasts via the lncRNA LURAP1L-AS1/LURAP1L/IKK/IκB/NF-κB signaling pathway [ Oncol Lett, 2021, 22(1):537]	PubMed: 34079593

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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