Tivozanib

製品コードS1207 バッチS120701

化学情報

	Synonyms	AV-951, KRN-951	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₂H₁₉ClN₄O₅
	分子量	454.86	CAS No.	475108-18-0
Solubility (25°C)*	体外	DMSO	45 mg/mL (98.93 mM)
		Water	Insoluble
		Ethanol	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	Tivozanib is a potent and selective VEGFR inhibitor for VEGFR1/2/3 with IC50 of 30 nM/6.5 nM/15 nM, and also inhibits PDGFR and c-Kit, low activity observed against FGFR-1, Flt3, c-Met, EGFR and IGF-1R. Phase 3.
in vitro	AV-951 is a novel quinoline-urea derivative. AV-951 blocks VEGF-dependent activation of mitogen-activated protein kinases and proliferation of endothelial cells. ^[1]
in vivo	In vivo studies show that AV-951 also decreases the micro vessel density and suppresses VEGFR2 phosphorylation levels in tumor xenografts, especially at a concentration of 1mg/kg (p.o. administration). AV-951 shows almost complete inhibition of tumor xenografts growth (TGI>85%) in athymic rats. ^[1] Another study in rat peritoneal disseminated tumor model shows that AV-951 could prolong the survival of the tumor-bearing rats with the MST of 53.5 days. AV-951 displays antitumor activity against many human tumor xenografts including lung, breast, colon, ovarian, pancreas and prostate cancer. ^[2]

プロトコル(参考用のみ)

キナーゼアッセイ	Kinase Assays
キナーゼアッセイ	Cell-free kinase assays are done in quadruplicate with 1 μM ATP to determine the IC50 values of AV-951 against a variety of recombinant receptor and nonreceptor tyrosine kinases including VEGFR1, VEGFR2, VEGFR3, c-Kit, PDGFRβ, Flt-3 and FGFR1.
細胞アッセイ	細胞株	Human umbilical vein endothelial cells (HUVEC) and normal human dermal fibroblasts
	濃度	1 μM
	反応時間	15 minutes
	実験の流れ	Human umbilical vein endothelial cells (HUVEC) and normal human dermal fibroblasts-based assays are done to determine the ability of AV-951 to inhibit ligand-dependent phosphorylation of tyrosine kinase receptors. The cells are starved overnight in appropriate basic medium containing 0.5% fetal bovine serum (FBS). The cells are incubated for 1 hour following the addition of AV-951 or 0.1% DMSO, and then stimulated with the cognate ligand at 37 °C. Receptor phosphorylation is induced for 5 minutes except for VEGFR3 (10 minutes), c-Met (10 minutes), and c-Kit (15 minutes). All the ligands used in the assays are human recombinant proteins, except for VEGF-C, a rat recombinant protein. Following cell lysis, receptors are immunoprecipitated with appropriate antibodies and subjected to immunoblotting with phosphotyrosine. Quantification of the blots and calculation of IC50 values are carried ou
動物実験	動物モデル	A549 xenografts in Athymic rats (RH-rnu/rnu)
	投薬量	1 mg/kg
	投与方法	Oral administration

参考

カスタマーフィードバック

: Data from [Data independently produced by Cytometry A, 2014, 85(6), 537-47]

: Data from [Cell Physiol Biochem, 2013, 32(5), 1541-50]

: ,

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：

ZDHHC2-Mediated AGK Palmitoylation Activates AKT-mTOR Signaling to Reduce Sunitinib Sensitivity in Renal Cell Carcinoma [ Cancer Res, 2023, 83(12):2034-2051]	PubMed: 37078777
Relevance of the organic anion transporting polypeptide 1B3 (OATP1B3) in the personalized pharmacological treatment of hepatocellular carcinoma [ Biochem Pharmacol, 2023, 214:115681]	PubMed: 37429423
Systematic identification of biomarker-driven drug combinations to overcome resistance [ Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7]	PubMed: 35332332
Impairment of the Retinal Endothelial Cell Barrier Induced by Long-Term Treatment with VEGF-A165 No Longer Depends on the Growth Factor's Presence [ Biomolecules, 2022, 12(5)734]	PubMed: 35625661
Impairment of the Retinal Endothelial Cell Barrier Induced by Long-Term Treatment with VEGF-A165 No Longer Depends on the Growth Factor's Presence [ Biomolecules, 2022, 12(5)734]	PubMed: 35625661
Kinase activity profiling in renal cell carcinoma, benign renal tissue and in response to four different tyrosine kinase inhibitors [ Oncotarget, 2022, 13:970-981]	PubMed: 36093296
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
Beovu, but not Lucentis impairs the function of the barrier formed by retinal endothelial cells in vitro [ Sci Rep, 2022, 12(1):12493]	PubMed: 35864147
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
Establishment and characterization of the NCC-GCTB4-C1 cell line: a novel patient-derived cell line from giant cell tumor of bone [ Hum Cell, 2021, 10.1007/s13577-021-00639-4]	PubMed: 34731453

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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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