Vatalanib (PTK787) 2HCl

製品コードS1101 バッチS110102

化学情報

	Synonyms	ZK 222584 (cpg-79787) 2HCl	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₀H₁₅ClN₄.2HCl
	分子量	419.73	CAS No.	212141-51-0
Solubility (25°C)*	体外	DMSO	85 mg/mL warmed with 50ºC water bath (202.51 mM)
		Water	10 mg/mL (23.82 mM)
		Ethanol	6 mg/mL (14.29 mM)
* <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	Vatalanib 2HCl (PTK787, ZK 222584, cpg-79787) is an inhibitor of VEGFR2/KDR with IC50 of 37 nM in a cell-free assay, less potent against VEGFR1/Flt-1, 18-fold against VEGFR3/Flt-4. Phase 3.
in vitro	Vatalanib also inhibits Flk, c-Kit and PDGFRβ with IC50 of 270 nM, 730 nM and 580 nM, respectively. Furthermore, Vatalanib shows the anti-proliferation effect by inhibiting thymidine incorporation induced by VEGF in HUVECs with and IC50 of 7.1 nM, and dose-dependently suppresses VEGF-induced survival and migration of endothelial cells in the same dose range without cytotoxic or antiproliferative effect on cells that do not express VEGF receptors. ^[1] A recent study shows that Vatalanib significantly inhibits the growth of hepatocellular carcinoma cells and enhances the IFN/5-FU induced apoptosis by increasing proteins levels of Bax and reduced Bcl-xL and Bcl-2. ^[2]
in vivo	Vatalanib induces dose-dependent inhibition of the angiogenic response to VEGF and PDGF in both a growth factor implant model and a tumor cell-driven angiogenesis model after once-daily oral dosing (25-100 mg/kg). In the same dose range, Vatalanib also inhibits the growth and metastasesof several human carcinomas in nude mice without significant effect on circulating blood cells or bone marrow leukocytes. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	VEGF Receptor Tyrosine Kinase Assays
キナーゼアッセイ	The in vitro kinase assays are performed in 96-well plates as a filter binding assay, using the recombinant GST-fused kinase domains expressed in baculovirus and purified over glutathione-Sepharose. γ-[³³P]ATP is used as the phosphate donor, and poly-(Glu:Tyr 4:1) peptide is used as the acceptor. Recombinant GST-fusion proteins are diluted in 20 mM Tris·HCl (pH 7.5) containing 1–3 mM MnCl₂, 3–10 mM MgCl₂, 0.25 mg/mL polyethylene glycol 20000, and 1 mM DTT, according to their specific activity. Each GST-fused kinase is incubated under optimized buffer conditions [20 mM Tris-HCl buffer (pH 7.5), 1–3 mM MnCl₂, 3–10 mM MgCl₂, 3–8 μg/mL poly-(Glu:Tyr 4:1), 0.25 mg/mL polyethylene glycol 20000, 8 μM ATP, 10 μM sodium vanadate, 1 mM DTT, and 0.2 μCi[γ-₃₃P]ATP in a total volume of 30 μL in the presence or absence of a test substance for 10 minutes at ambient temperature. The reaction is stopped by adding 10 μL of 250 mM EDTA. Using a 96-well filter system, half the volume (20 μL) is transferred onto a Immobilon-polyvinylidene difluoride membrane. The membrane is then washed extensively in 0.5% H₃PO₄ and then soaked in ethanol. After drying, Microscint cocktail is added, and scintillation counting is performed. IC50s for PTK787/ZK 222584 or SU5416 in these as well as all assays described below are calculated by linear regression analysis of the percentage inhibition.
細胞アッセイ	細胞株	HUVECs
	濃度	0-10 μM
	反応時間	48 hours
	実験の流れ	As a test of the ability of PTK787/ZK 222584 to inhibit a functional response to VEGF, an endothelial cell proliferation assay, based on BrdUrd incorporation is used. Subconfluent HUVECs are seeded into 96-well plates coated with 1.5% gelatin and then incubated at 37 °C and 5% CO₂ in growth medium. After 24 hours, growth medium is replaced by basal medium containing 1.5% FCS and a constant concentration of VEGF (50 ng/mL), bFGF (0.5 ng/mL), or FCS (5%), in the presence or absence of PTK787/ZK 222584. As a control, wells without growth factor are also included. After 24 hours of incubation, BrdUrd labeling solution is added, and cells incubated an additional 24 hours before fixation, blocking, and addition of peroxidase-labeled anti-BrdUrd antibody. Bound antibody is then detected using 3,3′5,5′-tetramethylbenzidine substrate, which results in a colored reaction product that is quantified spectrophotometrically at 450 nm.
動物実験	動物モデル	A431 epithelial carcinoma, Ls174T colon carcinoma, HT-29 colon carcinoma, PC-3 prostate carcinoma, DU145 prostate carcinoma, and CWR-22 prostate carcinoma cells are injected s.c. into the nude mice.
	投薬量	25-100 mg/kg
	投与方法	Administered via p.o.

参考

カスタマーフィードバック

: Data from [Data independently produced by Development, 2013, 140, 4323-34]

: Data from [Cell Res, 2011, 21, 1080-1087]

: Data from [Circ Res, 2011, 108, 1190-1198]

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：

Platform combining statistical modeling and patient-derived organoids to facilitate personalized treatment of colorectal carcinoma [ J Exp Clin Cancer Res, 2023, 42(1):79]	PubMed: 37013646
Inhibition of VEGFR2 and EGFR signaling cooperatively suppresses the proliferation of oral squamous cell carcinoma [ Cancer Med, 2023, 12(15):16416-16430]	PubMed: 37341071
Inhibition of VEGFR2 and EGFR signaling cooperatively suppresses the proliferation of oral squamous cell carcinoma [ Cancer Med, 2023, 12(15):16416-16430]	PubMed: 37341071
Investigation of the pharmacological effect and mechanism of mountain-cultivated ginseng and garden ginseng in cardiovascular diseases based on network pharmacology and zebrafish experiments [ Front Pharmacol, 2022, 13:920979]	PubMed: 36120313
In Vitro Angiogenesis Inhibition and Endothelial Cell Growth and Morphology [ Int J Mol Sci, 2022, 23(8)4277]	PubMed: 35457095
Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei [ J Pers Med, 2022, 12(2)258]	PubMed: 35207746
Establishment and characterization of NCC-UPS4-C1: a novel cell line of undifferentiated pleomorphic sarcoma from a patient with Li-Fraumeni syndrome [ Hum Cell, 2022, 10.1007/s13577-022-00671-y]	PubMed: 35118583
Prognostic Analysis of LncRNA MCM3AP-AS1 in Colorectal Cancer and the Mechanism of Its Effect on Tumor Cell Activity [ Biomed Res Int, 2022, 2022:1616370]	PubMed: 36172487
Rational application of gefitinib in NSCLC patients with sensitive EGFR mutations based on pharmacokinetics and metabolomics [ Acta Pharmacol Sin, 2021, 10.1038/s41401-021-00791-5]	PubMed: 34737420
Establishment and characterization of novel patient-derived cell lines from giant cell tumor of bone [ Hum Cell, 2021, 10.1007/s13577-021-00579-z]	PubMed: 34304386

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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