Regorafenib

製品コードS1178 バッチS117804

化学情報

	Synonyms	Fluoro-Sorafenib, BAY 73-4506	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₁H₁₅ClF₄N₄O₃
	分子量	482.82	CAS No.	755037-03-7
Solubility (25°C)*	体外	DMSO	97 mg/mL (200.9 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	Regorafenibは VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit (c-Kit), RET (c-RET) および Raf-1 に対するマルチターゲット阻害剤であり、cell-free assay における IC50 はそれぞれ 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM, 2.5 nM です。Regorafenib はオートファジーを誘導します。
in vitro	Regorafenib strongly prevents VEGFR2 autophosphorylation in NIH-3T3/VEGFR2 cells with IC50 of 3 nM. In HAoSMCs, regorafenib suppresses PDGFR-β autophosphorylation after stimulation with PDGF-BB, with an IC50 of 90 nM. Regorafenib also inhibits FGFR signaling in MCF-7 breast cancer (BC) cells stimulated with FGF10. Regorafenib very potently inhibited the mutant receptors KIT^K642E and RET^C634W, with IC50 of approximately 20 nM and 10 nM, respectively. Regorafenib inhibits the proliferation of VEGF¹⁶⁵-stimulated HUVECs, with an IC50 of approximately 3 nM. Regorafenib prevents the proliferation of FGF2-stimulated HUVECs and of PDGF-BB-stimulated HAoSMCs with IC50 of 127 nM and 146 nM, respectively. ^[1] Regorafenib targets both tumor cell proliferation and tumor vasculature through inhibition of receptors of tyrosine kinases (VEGFR, KIT, RET, FGFR, and PDGFR) and serine/threonine kinases (Raf and p38MAPK). ^[2] Regorafenib suppresses growth of human Hep3B, PLC/PRF/5 and HepG2 cells in a concentration- and time-dependent manner. ^[3]
in vivo	Regorafenib reveals potent dose-dependent TGI in various preclinical human xenograft models in mice, with tumor shrinkages in breast MDA-MB-231 and renal 786-O carcinoma models. Regorafenib prevents not only the growth of syngeneic primary 4T1 breast tumors growing orthotopically in the fat pad, but also suppresses the formation of tumor metastasis in the lung. ^[1]

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	In vitro assays using recombinant VEGFR2 (murine aa785–aa1367), VEGFR3 (murine aa818–aa1363), PDGFRβ (aa561–aa1106), Raf-1 (aa305–aa648) and BRafV600E (aa409–aa765) kinase domains are performed. Initial in vitro kinase inhibition profiling is performed at a fixed 1 μM Regorafenib concentration. Inhibitory concentration of 50% (IC50) values are determined from selected responding kinases, e.g., VEGFR1 and RET. TIE2 kinase inhibition is measured with a homogeneous time-resolved fluorescence (HTRF) assay using a recombinant fusion protein of glutathione-S-transferase, the intracellular domain of TIE2 and the peptide biotin-Ahx-EPKDDAYPLYSDFG as substrate.
細胞アッセイ	細胞株	GIST 882 and TT cells
	濃度	5 nM-10 μM
	反応時間	96 hours
	実験の流れ	For proliferation assays, GIST 882 and TT cells are grown in RPMI medium containing L-glutamine, and MDA-MB-231, HepG2 and A375 cells in DMEM always containing 10% hiFBS. Cells are trypsinized, plated at 5×10⁴ cells/well in 96-well plates in complete media containing 10% FBS and grown overnight at 37 °C. The next day, vehicle or Regorafenib serially diluted in complete growth media to between 10 μM and 5 nM final concentrations, and 0.2% DMSO, is added and incubation is continued for 96 hours. Cell proliferation is quantified.
動物実験	動物モデル	Female athymic NCr nu/nu mice with Colo-205, MDA-MB-231 or 786-O
	投薬量	3 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg
	投与方法	Orally

参考

カスタマーフィードバック

: Data from [Data independently produced by , , J Cell Physiol, 2015, 230(9): 2281-98]

: Data from [Data independently produced by , , Clin Cancer Res, 2014, 20(22):5768-76]

: Data from [Data independently produced by , , Naunyn Schmiedebergs Arch Pharmacol, 2017, 390(11):1125-1134]

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：

Regorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial [ Nat Med, 2024, 10.1038/s41591-024-02824-y]	PubMed: 38374347
Spatiotemporally resolved colorectal oncogenesis in mini-colons ex vivo [ Nature, 2024, 629(8011):450-457]	PubMed: 38658753
Targeting PDGF signaling of cancer-associated fibroblasts blocks feedback activation of HIF-1α and tumor progression of clear cell ovarian cancer [ Cell Rep Med, 2024, S2666-3791(24)00201-5]	PubMed: 38670097
A functional personalised oncology approach against metastatic colorectal cancer in matched patient derived organoids [ NPJ Precis Oncol, 2024, 8(1):52]	PubMed: 38413740
Upregulation of LHPP by saRNA inhibited hepatocellular cancer cell proliferation and xenograft tumor growth [ PLoS One, 2024, 19(5):e0299522]	PubMed: 38696452
Immuno-oncological effects of standard anticancer agents and commonly used concomitant drugs: an in vitro assessment [ BMC Pharmacol Toxicol, 2024, 25(1):25]	PubMed: 38444002
Immuno-oncological effects of standard anticancer agents and commonly used concomitant drugs: an in vitro assessment [ BMC Pharmacol Toxicol, 2024, 25(1):25]	PubMed: 38444002
Targeting PSAT1 to mitigate metastasis in tumors with p53-72Pro variant [ Signal Transduct Target Ther, 2023, 8(1):65]	PubMed: 36788227
Multiplexed kinase interactome profiling quantifies cellular network activity and plasticity [ Mol Cell, 2023, 83(5):803-818.e8]	PubMed: 36736316
Defining regorafenib as a senomorphic drug: therapeutic potential in the age-related lung disease emphysema [ Exp Mol Med, 2023, 55(4):794-805]	PubMed: 37009796

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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