Sorafenib

別名：NSC-724772,BAY 43-9006

製品コード：S7397 純度：99.89%

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.

CAS No. 284461-73-0

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
20mg	JPY 22000	国内在庫あり
50mg	JPY 40500	国内在庫あり
200mg	JPY 74500	国内在庫あり
1g	JPY 145500	国内在庫あり
2g	JPY 220500	国内在庫あり

代表番号: 045-509-1970\|電子メール：sales@selleck.co.jp よく尋ねられる質問

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製品安全説明書

現在のバッチを見る：純度： 99.89%

99.89

Sorafenib関連製品

関連ターゲット	C-Raf/Raf-1 B-Raf A-raf	もっと見る
関連製品	PLX-4720 LY3009120 AZ 628 GDC-0879 SB590885 TAK-632 RAF265 (CHIR-265) GW5074 Avutometinib PLX7904 Plixorafenib (PLX8394) ZM 336372 Naporafenib (LXH254) Lifirafenib (BGB-283) Agerafenib (CEP-32496) Tovorafenib (MLN2480) Belvarafenib B-Raf inhibitor 1 (Compound 13) dihydrochloride RAF709 CCT196969	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library MAPK Inhibitor Library Cell Cycle compound library TGF-beta/Smad compound library Anti-alzheimer Disease Compound Library	もっと見る

シグナル伝達経路

Rafシグナル伝達経路

Raf阻害剤の選択性比較

阻害剤	Citation	EGFR/ErbB1	HER2/ErbB2	ErbB3	ErbB4	mutant EGFR	その他
Saracatinib (AZD0530)	299	+++					c-Src,c-YES,LCK
Canertinib (CI-1033)	48	++++	+++
AG-490	132	+					JAK2 (V617F)
CP-724714	108		++
WZ4002	34	++++
Sapitinib (AZD8931)	48	+++	+++	+++
CUDC-101	23	+++	++				HDAC,HDAC1,HDAC6
AG-1478	97	+++
PD153035 HCl	17	++++
Pelitinib (EKB-569)	11	+	+				Src,MEK/ERK,Raf
AEE788 (NVP-AEE788)	13	++++	+++		+		c-Abl,FLT1,c-Fms
AC480 (BMS-599626)	10	++	++		+
AP26113-analog (ALK-IN-1)	4					++	ALK,IGF1R,INSR
WZ3146	2	++++
Allitinib tosylate	16	++++	+++		++++
Rociletinib (CO-1686)	36	++
Varlitinib	8	+++	++++
Icotinib (BPI-2009H)	9	+++
TAK-285	4	++	++		+		MEK1,Aurora B,LCK
WHI-P154	11	+++					Src,VEGFR,JAK3
Daphnetin	4	+					PKA,PKC
PD168393	6	++++
CNX-2006	2	++				++
Tyrphostin 9	1	+					PDGFR
AG-18	1	+
Icotinib Hydrochloride	0	+++
HS-10296 hydrochloride	0					++++
MTX-531	0	++					PI3Kα
Avitinib maleate	0	+++				++++	BTK
limertinib	0					++++
AG 825	0		+				PDGFR
4-AMino-1-phenylpyrazolo[3,4-d]pyriMidine	0	+
AST-1306	0	++++	+++		++++
ErbB2 inhibitor	0		+		+
Tuxobertinib (BDTX-189)	2	++++	++++				RIPK2,BLK
Epertinib hydrochloride	0	++++	+++		+++
JND3229	0	+++				++	EGFR C797S
BI-4020	1					++++
Tyrphostin AG-528	0	+	+
AG 556	0	+
Canertinib dihydrochloride	8	+++	+++
EGFR Inhibitor	3	++					Microtubules
SU5214	0	+					VEGFR2
RG 13022	0	+
TQB3804	0					++++
zipalertinib (TAS6417)	3	+++			+++	++++	TXK,BMX
Pyrotinib dimaleate	4	++	++
PD153035	14	++++
AG 494	0	+
AG 555	0	+
Theliatinib (HMPL-309)	0	+++				++
Avitinib (Abivertinib)	2					++++	JAK3,BTK
Lazertinib	7	++++				++++	Del19,L85R
Lifirafenib (BGB-283)	6	++				+	WT A-RAF,C-RAF (Y340/341D),BRAF(V600E)
Nazartinib (EGF816)	6	++				++
Zorifertinib (AZD3759)	6	++++
CL-387785 (EKI-785)	5	++++
Poziotinib	34	+++	+++		++
AZ5104	4	++++			+++		ACK1,BLK,BRK
AV-412 free base	0	++++	++			++++
HER2-Inhibitor-1	1		✔
WZ8040	2	✔
Genistein	32	✔					topo II
Rezivertinib	0	✔
BDTX-1535	0	✔
Falnidamol	0	✔
BLU-945	0	✔
(S)-Sunvozertinib ((S)-DZD9008)	1	✔
Licochalcone D	0	✔					NF-κB,PARP,Caspase
Alflutinib (Furmonertinib) mesylate	2	✔					CYP3A4
(Rac)-JBJ-04-125-02	0	✔
Tyrphostin AG30 (AG30)	0	✔
AG-1557	0	✔
AG99	0	✔
MTX-211	2	✔					PI3K
RG14620	0	✔					ABCG2
Almonertinib (HS-10296)	2					✔
Cyasterone	1	✔
Norcantharidin	3	✔					c-Met
Naquotinib(ASP8273)	1	✔
EAI045	2					✔
Olmutinib (BI 1482694)	5	✔					BTK
Butein	2	✔
Chrysophanic Acid	3	✔					mTOR
EGCG ((-)-Epigallocatechin Gallate)	41	✔					DNMT,telomerase,FASN

1. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation. 2. "✔" indicates inhibitory effect, but without specific value.

Cell Data

Cell Lines	Assay Type	活性情報	PMID
OS-RC-2	Growth Inhibition Assay	IC50=9.11243 μM	SANGER
LC-1F	Growth Inhibition Assay	IC50=9.10834 μM	SANGER
TE-10	Growth Inhibition Assay	IC50=8.76353 μM	SANGER
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

Targets

Raf-1 ^[1] (Cell-free assay)	mVEGFR2(Flk1) ^[1] (Cell-free assay)	mVEGFR3 ^[1] (Cell-free assay)	B-Raf ^[1] (Cell-free assay)	B-Raf (V599E) ^[1] (Cell-free assay)	もっとクリックする
6 nM	15 nM	20 nM	22 nM	38 nM	もっとクリックする

In Vitro
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]
Kinase Assay	Biochemical assays
Kinase Assay	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.
細胞実験	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.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	LC3-I / LC-3II / ATG5 p-STAT3 / STAT3 / Mcl-1 β-catenin / Survivin / Mcl-1 / PTMA pERK / ERK p-PKM2(y105) / PMK2 / Caspase-9 RET(pY1016) / VEGFR2(pY1214) / MEK1(pT292) / ERK(pY204) Cyclin D1		23392173
	Growth inhibition assay	Cell viability		26039995
	Immunofluorescence	p65 cytochrome c		22286758
	ELISA	TGF-beta / CD206 Caspase-9 / Caspase-3		26158762

In Vivo
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]
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
	投与量	~60 mg/kg
	投与経路	Orally once daily

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05068752	Recruiting	Pancreas Cancer	HonorHealth Research Institute\|Bayer\|Genentech Inc.	October 28 2021	Phase 2
NCT04763408	Active not recruiting	Carcinoma Hepatocellular	Eisai Inc.	April 9 2021	--

参考
[1] Wilhelm SM, et al. Cancer Res, 2004, 64(19), 7099-7109. [2] Liu L, et al. Cancer Res, 2006, 66(24), 11851-11858. [3] Ricci MS, et al. Cancer Cell, 2007, 12(1), 66-80.

参考

化学情報

分子量	464.82	化学式	C₂₁H₁₆ClF₃N₄O₃
CAS No.	284461-73-0	SDF	Download Sorafenib SDFをダウンロードする
Smiles	CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	１ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 93 mg/mL ( (200.07 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo Batch: Add solvents to the product individually and in order.					投与溶液組成計算機
	Clear solution	5%DMSO 1 Corn oil	5.0mg/ml (10.76mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.	投与溶液組成計算機
Clear solution	5%DMSO 1 40%PEG300 Click to order 2 5%Tween 80 Click to order 3 50%ddH2O	2.5mg/ml (5.38mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 45%PEG400 Click to order 2 50%ddH2O	0.38mg/ml (0.82mM)	Taking the 1 mL working solution as an example, add 50 μL of 7.5 mg/ml clarified DMSO stock solution to 450 μL of PEG 400, mix evenly to clarify it; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil	0.5mg/ml (1.08mM)	Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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