Cabozantinib (XL184)

製品コードS1119 バッチS111911

化学情報

	Synonyms	BMS-907351	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₈H₂₄FN₃O₅
	分子量	501.51	CAS No.	849217-68-1
Solubility (25°C)*	体外	DMSO	100 mg/mL (199.39 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	カボザンチニブ (Cabozantinib (XL184, BMS-907351)) は強力な VEGFR2 阻害剤であり、IC50 は 0.035 nM です。また c-Met, Ret, Kit, Flt-1/3/4, Tie2 および AXL に対しても阻害活性があり、cell-free assay における IC50 はそれぞれ 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM, 7 nM です。カボザンチニブは大腸がん細胞において AKT/GSK-3β/NF-κB 経路を介して PUMA 依存性アポトーシス (PUMA-dependent apoptosis) を誘発します。
in vitro	XL184 has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectivey, and has low activity against FGFR1 with IC50 of 5.294 μM. ^[1] XL184 at low concentration (0.1-0.5 μM) is sufficient to induce marked inhibition of constitutive and inducible Met phosphorylation and its resultant downstream signaling in MPNST cells, and inhibit HGF-induced MPNST cell migration and invasion. XL184 also induces marked inhibition of Met and VEGFR2 phosphorylation in cytokine-stimulated human umbilical vein endothelial cells (HUVECs). Although XL-184 has no significant effect on MPNST cell growth at 0.1 μM, XL184 at 5-10 μM significantly inhibits the MPNST cell growth. ^[2]
in vivo	XL184 treatment at 30 mg/kg in RIP-Tag2 mice with spontaneous pancreatic islet tumors disrupts 83% of the tumor vasculature, reduces pericytes and empty basement membrane sleeves, causes widespread intratumoral hypoxia and extensive tumor cell apoptosis, and slows regrowth of the tumor vasculature after drug withdrawal, more significantly compared with XL999 that blocks VEGFR but not c-Met, leading to only 43% reduction in vascularity, suggesting that concurrent inhibition of VEGFR and other functionally relevant receptor tyrosine kinases (RTK) amplifies angiogenesis inhibition. XL184 also decreases invasiveness of primary tumors and reduces metastasis. ^[1] XL184 at 30 mg/kg/day significantly abrogates human MPNST xenografts growth and metastasis in SCID mice. ^[2] Administration of XL184 induces dose-dependent inhibition of tumor growth in breast, lung, and glioma tumor models, in association with decreased tumor and endothelial cell proliferation as well as increased apoptosis. A single oral dose of XL184 is sufficient to induce sustained tumor growth inhibition in MDA-MB-231 tumor-bearing mice and C6 tumor-bearing rats at 100 mg/kg and 10 mg/kg, respectively. ^[3]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	ST88-14, STS26T, and MPNST724
	濃度	Dissolved in DMSO, final concentrations ~10 μM
	反応時間	48 hours
	実験の流れ	Cells are exposed to various concentrations of XL184 for 48 hours. Cell growth is determined by MTS assays using CellTiter96 Aqueous Non-Radioactive Cell Proliferation Assay kit. Absorbance is measured at a wavelength of 490 nm, and the absorbance values of treated cells are presented as a percentage of the absorbance of untreated cells.
動物実験	動物モデル	RIP-Tag2 transgenic mice in a C57BL/6 background with spontaneous pancreatic islet tumors
	投薬量	~60 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 Cancer Discov, 2014, 4(7), 816-27]

: Data from [Cell Death Dis, 2014, 5, e1471]

: Data from [Data independently produced by Liver Int, 2014, 10.1111/liv.12524]

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：

Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations [ Nat Cancer, 2023, 4(9):1345-1361]	PubMed: 37743366
Multiplexed kinase interactome profiling quantifies cellular network activity and plasticity [ Mol Cell, 2023, 83(5):803-818.e8]	PubMed: 36736316
Anti-hepatocellular carcinoma activity of the cyclin-dependent kinase inhibitor AT7519 [ Biomed Pharmacother, 2023, 164:115002]	PubMed: 37311277
Impact of tumor suppressor genes inactivation on the multidrug resistance phenotype of hepatocellular carcinoma cells [ Biomed Pharmacother, 2023, 165:115209]	PubMed: 37499450
Relevance of the organic anion transporting polypeptide 1B3 (OATP1B3) in the personalized pharmacological treatment of hepatocellular carcinoma [ Biochem Pharmacol, 2023, 214:115681]	PubMed: 37429423
Role of organic cation transporter 3 (OCT3) in the response of hepatocellular carcinoma to tyrosine kinase inhibitors [ Biochem Pharmacol, 2023, 217:115812]	PubMed: 37722628
Validation of miRNAs as diagnostic and prognostic biomarkers, and possible therapeutic targets in medullary thyroid cancers [ Front Endocrinol (Lausanne), 2023, 14:1151583]	PubMed: 37361540
Cabozantinib inhibits HBV-RNA transcription by decreasing STAT3 binding to the enhancer region of cccDNA [ Hepatol Commun, 2023, 10.1097/HC9.0000000000000313]	PubMed: 37938099
Cabozantinib in neuroendocrine tumors: tackling drug activity and resistance mechanisms [ Endocr Relat Cancer, 2023, 10.1530/ERC-23-0232]	PubMed: 37855330
A functional sgRNA-CRISPR screening method for generating murine RET and NTRK1 rearranged oncogenes [ Biol Open, 2023, 12(8)bio059994]	PubMed: 37470475

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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