Sorafenib (Bay 43-9006) tosylate is a potent oral active multikinase inhibitor. Sorafenib blocks autophosphorylation and activity of receptor tyrosine kinases (VEGFR-2, VEGFR-3) and RAF family kinases, thereby suppressing the RAF/MEK/ERK and PI3K/Akt pathways, inhibiting STAT3 phosphorylation, and selectively inhibiting the MAPK pathway in cancer cells. Sorafenib tosylate induces cell cycle arrest, autophagy, apoptosis, and PARP cleavage, reduces Bcl-2, Bcl-XL, cyclin D1 levels, and activates Bak and Bax. Sorafenib tosylate inhibits tumor growth and metastasis in mouse and rat models. Sorafenib tosylate can be used for cancer research, such as colon, breast, non-small-cell lung cancer (NSCLC), ovarian, pancreatic, melanoma, colorectal and hepatocellular carcinoma^{[1][2][3][4][5][6]}.

Sorafenib (0.01-3 μM; 2 h) tosylate selectively inhibits the MAPK pathway, while has no effect on the PKB pathway in MDA-MB-231 cells^[1].
Sorafenib (0.01-15 μM; 2 h) tosylate inhibits MEK 1/2 and ERK 1/2 phosphorylation in MDA-MB-231 human breast carcinoma cells (IC₅₀s of 40 and 90 nmol/L, respectively), ERK 1/2 phosphorylation in BxPC-3, LOX, HCT 116, HT-29, Colo-205, and Mia PaCa-2 cells, but does not inhibit ERK 1/2 phosphorylation in A549 and NCI-H460 cells^[1].
Sorafenib (0.01-10 μM; 72 h) tosylate inhibits proliferation of MDA-MB-231 cells with an IC₅₀ of 2600 nmol/L)^[1].
Sorafenib (8.9 μM) tosylate exhibits an IC₅₀ of 8.9 μM in human colorectal carcinoma HCT8 and HT29 cell lines, and causes marked antagonism with oxaliplatin and cisplatin across all tested incubation schedules, reducing platinum-induced cytotoxicity^[2].
Sorafenib (4-24 μM; 24 h) tosylate reduces expression of p21^Cip1 protein and cyclin D1 expression in HCT8 and HT29 cells when incubated simultaneously with Oxaliplatin (HY-17371) or Cisplatin (HY-17394)^[2].
Sorafenib (24 μM; 4 h) tosylate significantly reduces Cisplatin- and Oxaliplatin-induced DNA adduct levels in HCT8 and HT29 cells when applied simultaneously, but does not affect adduct levels or repair when applied consecutively^[2].
Sorafenib (0-20 μmol/L; 24-72 h) tosylate inhibits the proliferation of HCCLM3, HepG2, and rat Morris hepatoma 3924A (MH) HCC cell lines in a time- and dose-dependent manner^[3].
Sorafenib (0-20 μmol/L; 2-24 h) tosylate durably inhibits phosphorylation of STAT3^Y705 and ^S727, ERK1/2, and Akt, and reduces cyclin D1 expression, without altering JAK2 or SHP2 phosphorylation, in HCCLM3, HepG2, and MH HCC cell lines^[3].
Sorafenib (5 μM; 48 h) tosylate significantly increases clonogenicity, enhances tumoursphere formation, and upregulates cancer stem cell-associated pluripotency markers Sox2 and Oct4 in A549, NCI-H460, and NCI-H1299 NSCLC cells^[5].
Sorafenib (5 μM; 48 h) tosylate increases ALDH-positive cancer stem cell populations in A549 NSCLC cells^[5].
Sorafenib (5 μM; 48 h) tosylate significantly enhances migration capacity in NCI-H460 NSCLC cells^[5].
Sorafenib (5 μM; 48 h) tosylate induces epithelial-to-mesenchymal transition in NCI-H460 NSCLC cells via downregulation of E-cadherin and upregulation of N-cadherin, vimentin, and MMP2, and activates the AKT pathway via increased AKT phosphorylation^[5].
Sorafenib (5 μM; 48 h) tosylate upregulates STMN1, FOXM1, and E2F1 expression at the mRNA and protein levels in NCI-H460 and NCI-H1299 NSCLC cells^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Sorafenib (7.5-60 mg/kg; p.o.; daily for 5 or 9 days) tosylate inhibits tumor growth, suppresses RAF/MEK/ERK signaling, and reduces angiogenesis in mouse breast, colon, and NSCLC xenograft models, with no observed toxicity^[1].
Sorafenib (30 mg/kg; i.g.; once daily; once daily from day 17 to day 38) tosylate inhibits hepatocellular carcinoma tumor growth and metastasis in an orthotopic rat Morris Hepatoma (MH) model, while inducing tumor apoptosis and suppressing STAT3, Akt, and ERK phosphorylation^[3].
Sorafenib (10 mg/kg; p.o.; daily; 2 weeks) tosylate exhibits antineoplastic activity in Diethyl Nitrosamin (DENA)-induced hepatocellular carcinoma in albino rats^[4].
Sorafenib (4 mg/kg; i.p.; twice a week for 4 weeks) tosylate in combined with intratumoral siTUC338 significantly reduces tumor volume in mouse HepG2/Sor xenografts via upregulation of RASAL1^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

637.03

C₂₈H₂₄ClF₃N₄O₆S

475207-59-1

Solid

White to off-white

O=S(C1=CC=C(C=C1)C)(O)=O.O=C(NC2=CC=C(C(C(F)(F)F)=C2)Cl)NC3=CC=C(OC4=CC(C(NC)=O)=NC=C4)C=C3

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 1 year; -20°C, 6 months (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months (sealed storage, away from moisture). When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

• [1]. Wilhelm SM, 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.  [Content Brief]

  [2]. Heim M, et al. The Raf kinase inhibitor BAY 43-9006 reduces cellular uptake of platinum compounds and cytotoxicity in human colorectal carcinoma cell lines. Anticancer Drugs. 2005;16(2):129-136.

  [3]. Gu FM, et al. Sorafenib inhibits growth and metastasis of hepatocellular carcinoma by blocking STAT3. World J Gastroenterol. 2011 Sep 14;17(34):3922-32.

  [4]. El-Ashmawy NE, et al. Sorafenib effect on liver neoplastic changes in rats: more than a kinase inhibitor. Clin Exp Med. 2016 Apr 16.  [Content Brief]

  [5]. Li M, et al. Activation of an AKT/FOXM1/STMN1 pathway drives resistance to tyrosine kinase inhibitors in lung cancer. Br J Cancer. 2017;117(7):974-983.  [Content Brief]

  [6]. Jin W, et al. Long non-coding RNA TUC338 is functionally involved in sorafenib-sensitized hepatocarcinoma cells by targeting RASAL1. Oncol Rep. 2017;37(1):273-280.  [Content Brief]