Sorafenib
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| カタログ番号GC17369 |
ソラフェニブは、Raf-1とB-Rafをターゲットとするマルチキナーゼ阻害剤であり、それぞれのIC50値は6 nMおよび22 nMです。
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Cas No.: 284461-73-0
Sample solution is provided at 25 µL, 10mM.
Sorafenib acts as a multi-kinase inhibitor, targeting Raf-1 and B-Raf with IC50 values of 6 nM and 22 nM, respectively. Additionally, Sorafenib demonstrates inhibitory effects on VEGFR-2, VEGFR-3, PDGFR-β, Flt-3, and c-KIT, displaying corresponding IC50 values of 90 nM, 20 nM, 57 nM, 59 nM, and 68 nM. Beyond these kinase activities, Sorafenib is capable of inducing autophagy and apoptosis while triggering ferroptosis activation, resulting in its notable antitumor efficacy [1-3].
Sorafenib(5-40μM; 24 h) had a dose-dependent inhibitory effect on HSC-T6 cells viability [4]. Sorafenib(25mM;0-42h) alters the lipid composition in Huh7.5 cells[5].
Sorafenib(2.5, 5, 10 mg/kg; i.p; twice a week for 8 weeks) attenuated liver injury and extracellular matrix (ECM) accumulation in CCl4 -induced fibrotic livers, accompanied by reduction of SLC7A11 and GPX4 proteins[4]. Treatment with erastin and sorafenib(10 mg/kg; i.p; once every other day) alleviated liver fibrosis in mice by inducing hepatic stellate cells(HSCs) ferroptosis in mice[6].The synergism of sorafenib and T cells is mediated via reduced ATF4 expression, causing activation of the IRF7-IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans[7].
References:
[1]. Abdelgalil AA, Alkahtani HM, et,al.Sorafenib. Profiles Drug Subst Excip Relat Methodol. 2019;44:239-266. doi: 10.1016/bs.podrm.2018.11.003. Epub 2019 Jan 18. PMID: 31029219.
[2]. Wilhelm SM, Carter C, et,al.BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004 Oct 1;64(19):7099-109. doi: 10.1158/0008-5472.CAN-04-1443. PMID: 15466206.
[3]. Xia S, Pan Y, et,al.The microenvironmental and metabolic aspects of sorafenib resistance in hepatocellular carcinoma. EBioMedicine. 2020 Jan;51:102610. doi: 10.1016/j.ebiom.2019.102610. Epub 2020 Jan 6. PMID: 31918403; PMCID: PMC7000339.
[4]. Yuan S, Wei C, et,al. Sorafenib attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis via HIF-1α/SLC7A11 pathway. Cell Prolif. 2022 Jan;55(1):e13158. doi: 10.1111/cpr.13158. Epub 2021 Nov 22. PMID: 34811833; PMCID: PMC8780895.
[5]. Liu G, Kuang S, et,al.Sorafenib kills liver cancer cells by disrupting SCD1-mediated synthesis of monounsaturated fatty acids via the ATP-AMPK-mTOR-SREBP1 signaling pathway. FASEB J. 2019 Sep;33(9):10089-10103. doi: 10.1096/fj.201802619RR. Epub 2019 Jun 14. PMID: 31199678.
[6]. Zhang Z, Guo M, et,al. RNA-binding protein ZFP36/TTP protects against ferroptosis by regulating autophagy signaling pathway in hepatic stellate cells. Autophagy. 2020 Aug;16(8):1482-1505. doi: 10.1080/15548627.2019.1687985. Epub 2019 Nov 11. PMID: 31679460; PMCID: PMC7469536.
[7]. Mathew NR, Baumgartner F,et,al. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells. Nat Med. 2018 Mar;24(3):282-291. doi: 10.1038/nm.4484. Epub 2018 Feb 12. Erratum in: Nat Med. 2018 Apr 10;24(4):526. PMID: 29431743; PMCID: PMC6029618.
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In vitro Kinase Assays with Recombinant Raf-1, BRAF, V599E BRAF, MEK-1, and ERK1[1]: |
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Preparation method |
Test compound inhibition against various RAF kinase isoforms, sorafenib was added to a mixture of Raf-1 (80 ng), wt BRAF, or V599E BRAF (80 ng) with MEK-1 (1 μg) in assay buffer [20 mmol/L Tris (pH 8.2), 100 mmol/L NaCl, 5 mmol/L MgCl2, and 0.15% β-mercaptoethanol] at a final concentration of 1% DMSO. The RAF kinase assay (final volume of 50 μL) was initiated by adding 25 μL of 10 μmol/L γ-[33P]ATP (400 Ci/mol) and incubated at 32℃ for 25 minutes. Phosphorylated MEK-1 was harvested by filtration onto a phosphocellulose mat, and 1% phosphoric acid was used to wash away unbound radioactivity. After drying by microwave heating, a β-plate counter was used to quantify filter-bound radioactivity. |
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Applications |
Sorafenib inhibited Raf-1 with IC50 of 6nM; Sorafenib inhibited B-Raf activity of wild type and V599E mutant with IC50 of 22 nM and 38 nM, respectively; Sorafenib has no activity against ERK-1, MEK-1. |
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Cell experiment [2]: |
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Cell lines |
HSC-T6 cells |
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Preparation method |
Cells were seeded into 96-well plates. When the cell density reached 70%, different concentrations of sorafenib were added, and equal amounts of DMSO without drug were exposed to the control group for 24 h. |
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Reaction Conditions |
5-40μM; 24 h |
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Applications |
HSC-T6 cell viability was dose-dependently inhibited by sorafenib at concentrations ranging from 5 to 40 μM. |
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Animal experiment [2]: |
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Animal models |
Male C57BL/6 mice (6-8 weeks) |
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Preparation method |
Mice were randomly divided into five groups (n=6 per group) including the vehicle group, CCl4-treated group, CCl4 + sorafenib (2.5, 5, 10 mg/kg)-treated groups. The groups treated with CCl4, CCl4 + sorafenib were subjected intraperitoneal injections of olive oil with 10% CCl4 for 8 weeks to induce liver fibrosis. The vehicle group was subjected intraperitoneal injections of the same dose of olive oil. After 4 weeks, each mouse in the groups treated with CCl4 + sorafenib was orally administered sorafenib daily. The vehicle group and the CCl4-treated group were orally administered the same dose of saline daily. |
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Dosage form |
2.5, 5, 10 mg/kg; i.p; twice a week for 8 weeks |
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Applications |
Sorafenib attenuated liver injury and ECM accumulation in CCl4 -induced fibrotic livers. |
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References: [1]. Wilhelm SM, Carter C, et,al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004 Oct 1;64(19):7099-109. doi: 10.1158/0008-5472.CAN-04-1443. PMID: 15466206. [2]. Yuan S, Wei C, et,al.Sorafenib attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis via HIF-1α/SLC7A11 pathway. Cell Prolif. 2022 Jan;55(1):e13158. doi: 10.1111/cpr.13158. Epub 2021 Nov 22. PMID: 34811833; PMCID: PMC8780895. |
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| Cas No. | 284461-73-0 | SDF | |
| 同義語 | BAY 43-9006 | ||
| Chemical Name | 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide | ||
| Canonical SMILES | CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F | ||
| Formula | C21H16ClF3N4O3 | M.Wt | 464.82 |
| 溶解度 | ≥ 23.25mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1514 mL | 10.7569 mL | 21.5137 mL |
| 5 mM | 0.4303 mL | 2.1514 mL | 4.3027 mL |
| 10 mM | 0.2151 mL | 1.0757 mL | 2.1514 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
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Quality Control & SDS
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- Purity: >99.00%
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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