Sorafenib

製品コードS7397 バッチS739707

印刷

化学情報

Chemical Structure Synonyms NSC-724772,BAY 43-9006 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C21H16ClF3N4O3
分子量 464.82 CAS No. 284461-73-0
Solubility (25°C)* 体外 DMSO 92 mg/mL (197.92 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 Sorafenib is a multikinase inhibitor of Raf-1 and B-Raf with IC50 of 6 nM and 22 nM in cell-free assays, respectively. Sorafenib inhibits VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 and c-KIT with IC50 of 90 nM, 20 nM, 57 nM, 59 nM and 68 nM, respectively. Sorafenib induces autophagy and apoptosis and activates ferroptosis with anti-tumor activity.
in vitro Sorafenib inhibits both wild-type and V599E mutant B-Raf activity with IC50 of 22 nM and 38 nM, respectively. Sorafenib also potently inhibits mVEGFR2 (Flk-1), mVEGFR3, mPDGFRβ, Flt3, and c-Kit with IC50 of 15 nM, 20 nM, 57 nM, 58 nM, and 68 nM, respectively. Sorafenib weakly inhibits FGFR-1 with IC50 of 580 nM. Sorafenib tosylate is not active against ERK-1, MEK-1, EGFR, HER-2, IGFR-1, c-Met, PKB, PKA, cdk1/cyclinB, PKCα, PKCγ, and pim-1. Sorafenib markedly inhibits VEGFR2 phosphorylation in NIH 3T3 cells with IC50 of 30 nM, and Flt-3 phosphorylation in HEK-293 cells with IC50 of 20 nM. Sorafenib potently blocks MEK 1/2 and ERK 1/2 phosphorylation in most cell lines but not in A549 or H460 cells, while having no effect on inhibition of the PKB pathway. Sorafenib inhibits the proliferation of HAoSMC and MDA-MB-231 cells with IC50 of 0.28 μM and 2.6 μM, respectively. [1] In addition to inhibition of the RAF/MEK/ERK signaling pathway, Sorafenib significantly inhibits the phosphorylation of eIF4E and down-regulates Mcl-1 levels in hepatocellular carcinoma (HCC) cells in a MEK/ERK-independent manner. Sorafenib inhibits the proliferation of PLC/PRF/5 and HepG2 cells with IC50 of 6.3 μM and 4.5 μM, respectively, and leads to the significant induction of apoptosis. [2]
in vivo Oral administration of Sorafenib (~60 mg/kg) demonstrates broad spectrum, dose-dependent anti-tumor activity against a variety of human tumor xenograft models including MDA-MB-231, Colo-205, HT-29, DLD-1, NCI-H460, and A549, with no evidence of toxicity. In association with the anti-tumor efficacy, Sorafenib treatment potently inhibits MEK 1/2 phosphorylation and pERK 1/2 levels in HT-29 and MDA-MB-231 xenografts but not in Colo-205 xenografts, and significantly suppresses tumor microvessel area (MVA) and microvessel density (MVD) in MDA MB-231, HT-29 and Colo-205 tumor xenografts. [1] Sorafenib treatment produces dose-dependent growth inhibition of PLC/PRF/5 tumor xenografts in SCID mice with TGIs of 49% and 78% at 10 mg/kg and 30 mg/kg, respectively, consistent with the inhibition of ERK and eIF4E phosphorylation, reduction of the microvessel area, and induction of tumor cell apoptosis. [2] Sorafenib sensitizes bax-/- cells to TRAIL in a dose-dependent manner, through a mechanism involving down-regulating NF-κB mediated Mcl-1 and cIAP2 expression. Combining Sorafenib (30-60 mg/kg) with TRAIL (5 mg/kg) show dramatic efficacy in TRAIL-resistant HCT116 bax-/- and HT29 tumor xenografts. [3]

プロトコル(参考用のみ)

キナーゼアッセイ Biochemical assays
Recombinant baculoviruses expressing Raf-1 (residues 305–648) and B-Raf (residues 409–765) are purified as fusion proteins. Full-length human MEK-1 is generated by PCR and purified as a fusion protein from Escherichia coli lysates. Sorafenib tosylate is added to a mixture of Raf-1 (80 ng), or B-Raf (80 ng) with MEK-1 (1 μg) in assay buffer [20 mM Tris (pH 8.2), 100 mM NaCl, 5 mM MgCl2, and 0.15% β-mercaptoethanol] at a final concentration of 1% DMSO. The Raf kinase assay (final volume of 50 μL) is initiated by adding 25 μL of 10 μM γ[33P]ATP (400 Ci/mol) and incubated at 32 °C for 25 minutes. Phosphorylated MEK-1 is harvested by filtration onto a phosphocellulose mat, and 1% phosphoric acid is used to wash away unbound radioactivity. After drying by microwave heating, a β-plate counter is used to quantify filter-bound radioactivity. Human VEGFR2 (KDR) kinase domain is expressed and purified from Sf9 lysates. Time-resolved fluorescence energy transfer assays for VEGFR2 are performed in 96-well opaque plates in the time-resolved fluorescence energy transfer format. Final reaction conditions are as follows: 1 to 10 μM ATP, 25 nM poly GT-biotin, 2 nM Europium-labeled phospho (p)-Tyr antibody (PY20), 10 nM APC, 1 to 7 nM cytoplasmic kinase domain in final concentrations of 1% DMSO, 50 mM HEPES (pH 7.5), 10 mM MgCl2, 0.1 mM EDTA, 0.015% Brij-35, 0.1 mg/mL BSA, and 0.1% β-mercaptoethanol. Reaction volumes are 100 μL and are initiated by addition of enzyme. Plates are read at both 615 and 665 nM on a Perkin-Elmer VictorV Multilabel counter at ~1.5 to 2.0 hours after reaction initiation. Signal is calculated as a ratio: (665 nm/615 nM) × 10,000 for each well. For IC50 generation, Sorafenib tosylate is added before the enzyme initiation. A 50-fold stock plate is made with Sorafenib tosylate serially diluted 1:3 in a 50% DMSO/50% distilled water solution. Final Sorafenib tosylate concentrations range from 10 μM to 4.56 nM in 1% DMSO.
細胞アッセイ 細胞株 MDA-MB-231, and HAoSMC
濃度 Dissolved in DMSO, final concentrations ~10 μM
反応時間 72 hours
実験の流れ

Cells are exposed to increasing concentrations of Sorafenib tosylate for 72 hours. Cell number is quantitated using the Cell TiterGlo ATP Luminescent assay kit. This assay measures the number of viable cells per well by measurement of luminescent signal based on amount of cellular ATP.
動物実験 動物モデル Female NCr-nu/nu mice implanted s.c. with MDA-MB-231, Colo-205, HT-29, H460, or A549 cells
投薬量 ~60 mg/kg
投与方法 Orally once daily

カスタマーフィードバック

Data from [Data independently produced by Mol Cancer Res, 2014, 12(10), 1377-87]

Data from [Data independently produced by Apoptosis, 2014, 19(4), 682-97]

Data from [Data independently produced by J Neurosci, 2013, 33(7), 3079-93]

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：

Inhibition of PTPRE suppresses tumor progression and improves sorafenib response in hepatocellular carcinoma [ Biomed Pharmacother, 2024, 173:116366] PubMed: 38458013
Apigenin enhances sorafenib anti-tumour efficacy in hepatocellular carcinoma [ Transl Oncol, 2024, 43:101920] PubMed: 38394865
CircPHKB decreases the sensitivity of liver cancer cells to sorafenib via miR-1234-3p/CYP2W1 axis [ Genomics, 2024, 116(1):110764] PubMed: 38113974
Multiplexed kinase interactome profiling quantifies cellular network activity and plasticity [ Mol Cell, 2023, 83(5):803-818.e8] PubMed: 36736316
HSP90β Impedes STUB1-Induced Ubiquitination of YTHDF2 to Drive Sorafenib Resistance in Hepatocellular Carcinoma [ Adv Sci (Weinh), 2023, 10.1002/advs.202302025] PubMed: 37515378
HSP90β Impedes STUB1-Induced Ubiquitination of YTHDF2 to Drive Sorafenib Resistance in Hepatocellular Carcinoma [ Adv Sci (Weinh), 2023, 10(27):e2302025] PubMed: 37515378
A biomimetic liver cancer on-a-chip reveals a critical role of LIPOCALIN-2 in promoting hepatocellular carcinoma progression [ Acta Pharm Sin B, 2023, 13(11):4621-4637] PubMed: 37969730
Protein phosphatase 2A-B55β mediated mitochondrial p-GPX4 dephosphorylation promoted sorafenib-induced ferroptosis in hepatocellular carcinoma via regulating p53 retrograde signaling [ Theranostics, 2023, 13(12):4288-4302] PubMed: 37554285
Targeting fatty acid synthase modulates sensitivity of hepatocellular carcinoma to sorafenib via ferroptosis [ J Exp Clin Cancer Res, 2023, 42(1):6] PubMed: 36604718
Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer [ J Exp Clin Cancer Res, 2023, 42(1):142] PubMed: 37277863

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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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