Regorafenib (BAY 73-4506)

製品コードS1178 バッチS117809

印刷

化学情報

Chemical Structure 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 96 mg/mL (198.83 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 95% Corn oil

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 5.000mg/ml (10.36mM) Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <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, this compound suppresses PDGFR-β autophosphorylation after stimulation with PDGF-BB, with an IC50 of 90 nM. It also inhibits FGFR signaling in MCF-7 breast cancer (BC) cells stimulated with FGF10. This chemical very potently inhibited the mutant receptors KITK642E and RETC634W, with IC50 of approximately 20 nM and 10 nM, respectively. It inhibits the proliferation of VEGF165-stimulated HUVECs, with an IC50 of approximately 3 nM. This compound prevents the proliferation of FGF2-stimulated HUVECs and of PDGF-BB-stimulated HAoSMCs with IC50 of 127 nM and 146 nM, respectively. [1] It 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] This chemical 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. This compound 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
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 concentration of this compound. 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

  • https://pubmed.ncbi.nlm.nih.gov/21170960/
  • https://pubmed.ncbi.nlm.nih.gov/21789125/
  • https://pubmed.ncbi.nlm.nih.gov/22777740/

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：

S100P is a ferroptosis suppressor to facilitate hepatocellular carcinoma development by rewiring lipid metabolism [ Nat Commun, 2025, 16(1):509] PubMed: 39779666
The PLEKHA1-TACC2 fusion gene drives tumorigenesis via vascular mimicry formation in esophageal squamous-cell carcinoma [ Cell Death Differ, 2025, 10.1038/s41418-025-01536-1] PubMed: 40615663
Therapeutic Potential of STE20-Type Kinase STK25 Inhibition for the Prevention and Treatment of Metabolically Induced Hepatocellular Carcinoma [ Cell Mol Gastroenterol Hepatol, 2025, S2352-345X(25)00026-8] PubMed: 40024534
Exploiting collateral sensitivity in the evolution of resistance to tyrosine kinase inhibitors in soft tissue sarcomas [ Commun Biol, 2025, 8(1):1185] PubMed: 40781553
Relevance of transportome among the mechanisms of chemoresistance in hepatoblastoma [ Biochem Pharmacol, 2025, 237:116914] PubMed: 40185314
The SCD1 inhibitor aramchol interacts with regorafenib to kill GI tumor cells in vitro and in vivo [ Oncotarget, 2025, 16:662-678] PubMed: 40827882
Proteome changes associated with effect of high dose single-fractionation radiation on lung adenocarcinoma cell lines [ Sci Rep, 2025, 15(1):24245] PubMed: 40624183
Small molecule kinase inhibitor altiratinib inhibits brain cyst forming bradyzoites of Toxoplasma gondii [ J Microbiol, 2025, 63(2):e2409001] PubMed: 40044130
Fibroblasts drive differential response in immunotherapy via IL-6 in bioengineered 3D cancer constructs [ bioRxiv, 2025, 2025.06.18.660473] PubMed: 40667289
Regorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial [ Nat Med, 2024, 10.1038/s41591-024-02824-y] PubMed: 38374347

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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