 |
Sorafenib tosylate
- Iupac Name：4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-
methylpyridine-2-carboxamide; 4-methylbenzenesulfonic acid
- CAS No.: 475207-59-1
- Molecular Weight：637.02657
- Modify Date.: 2022-11-23 18:48
- Introduction: Sorafenib is available in 200-mg tablets for oral administrationand is used in the treatment of RCC and colon cancer.The agent is classified as a multikinase inhibitor because ofits action on numerous kinase enzymes including thePDGF-R, VEGF-R, Kit, and Raf. Sorafenib is 39% to 48% bioavailable and CYP3A4-mediated metabolism giveseight identified metabolites including the N-oxide, which isequally active with the parent. However, the majority of thedrug in plasma is present as the parent compound.Sorafenib is highly protein bound (99.5%). The drug iseliminated primarily in the feces (77%) with 19% appearingin the urine as glucuronides (UGT1A1) and has a eliminationhalf-life of 24 to 48 hours. The most commonly seentoxicity is skin rash that normally occurs within the first6 weeks of therapy. Other adverse effects include hypertension,fatigue, increased wound healing time, and increasedrisk of bleeding. Sorafenib tosylateSupplier
View more+
1. Names and Identifiers
- 1.1 Name
- Sorafenib tosylate
- 1.2 Synonyms
4-(4-(3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)-N2-methylpyridine-2-carboxamide mono (4-methylbenzenesulfonate) 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide,4-methylbenzenesulfonic acid 4-Methyl-3-((4-(3-pyridinyl)-2-pyrimidinyl)amino)-N-(5-(4-methyl-1H-imidazol-1-yl)-3-(trifluoromethyl)phenyl)benzamide monomethanesulfonate BAY 43-9006 BAY43-9006 Sorafenib & its intermediates Sorafenib (Tosylate) SORAFENIB TOSYLATE (BAY 43-9006 TOSYLATE) Sorafenib Tosylate(Bay 43-9006,Nexavar) Sorafinib mesylate
- View all
- 1.3 CAS No.
- 475207-59-1
- 1.4 CID
- 406563
- 1.5 EINECS(EC#)
- 641-758-8
- 1.6 Molecular Formula
- C28H24ClF3N4O6S (isomer)
- 1.7 Inchi
- InChI=1S/C21H16ClF3N4O3.C7H8O3S/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25;1-6-2-4-7(5-3-6)11(8,9)10/h2-11H,1H3,(H,26,30)(H2,28,29,31);2-5H,1H3,(H,8,9,10)
- 1.8 InChIkey
- IVDHYUQIDRJSTI-UHFFFAOYSA-N
- 1.9 Canonical Smiles
- CC1=CC=C(C=C1)S(=O)(=O)O.CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F
- 1.10 Isomers Smiles
- CC1=CC=C(C=C1)S(=O)(=O)O.CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F
2. Properties
- 2.1 Density
- 1.454
- 2.1 Melting point
- 240-243°C
- 2.1 Boiling point
- 523.3 °C at 760 mmHg
- 2.1 Flash Point
- 270.3 °C
- 2.1 Precise Quality
- 636.10600
- 2.1 PSA
- 155.10000
- 2.1 logP
- 8.40910
- 2.1 Appearance
- White to off-white crystalline powder
- 2.2 Color/Form
- Powder
- 2.3 StorageTemp
- 2-8°C(protect from light)
3. Use and Manufacturing
- 3.1 General Description
- Sorafenib is available in 200-mg tablets for oral administrationand is used in the treatment of RCC and colon cancer.The agent is classified as a multikinase inhibitor because ofits action on numerous kinase enzymes including thePDGF-R, VEGF-R, Kit, and Raf. Sorafenib is 39% to 48% bioavailable and CYP3A4-mediated metabolism giveseight identified metabolites including the N-oxide, which isequally active with the parent. However, the majority of thedrug in plasma is present as the parent compound.Sorafenib is highly protein bound (99.5%). The drug iseliminated primarily in the feces (77%) with 19% appearingin the urine as glucuronides (UGT1A1) and has a eliminationhalf-life of 24 to 48 hours. The most commonly seentoxicity is skin rash that normally occurs within the first6 weeks of therapy. Other adverse effects include hypertension,fatigue, increased wound healing time, and increasedrisk of bleeding. Sorafenib tosylateSupplier
- 3.2 Usage
- Sorafenib Tosylate (Bay 43-9006, Nexavar) is a small molecular inhibitor of VEGFR, PDGFR, c-Raf and B-Raf with IC50s of 18 nM, 10 nM, 3 nM and 15 nM, respectively.
4. Safety and Handling
- 4.1 Risk Statements
- 36/37/38
- 4.1 Safety Statements
- 28-26
- 4.1 Hazard Declaration
- H302
- 4.1 Caution Statement
- P201, P202, P260, P261, P264, P270, P271, P273, P281, P301+P312, P304+P312, P304+P340, P308+P313, P312, P314, P330, P405, P501
- 4.1 Specification
-
?Nexavar , its cas register number is 475207-59-1. It also can be called?Sorafenib tosylate [USAN]?; 1-(4-Chloro-3-(trifluoromethyl)phenyl)-3-(4-((2-(methylcarbamoyl)pyridin-4-yl)oxy)phenyl)urea mono(4-methylbenzenesulfonate) ; 4-(4-(3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)-N2-methylpyridine-2-carboxamide mono (4-methylbenzenesulfonate) ; BAY 43-9006 ; BAY43-9006 ; Nexavar(R) ; Sorafenib tosylate ; UNII-5T62Q3B36J ; 2-Pyridinecarboxamide, 4-(4-((((4-chloro-3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenoxy)-N-methyl-, mono(4-methylbenzenesulfonate) .
5. MSDS
2.Hazard identification
2.1 Classification of the substance or mixture
Reproductive toxicity, Category 1B
Specific target organ toxicity \u2013 repeated exposure, Category 2
2.2 GHS label elements, including precautionary statements
| Pictogram(s) |  |
| Signal word | Danger |
| Hazard statement(s) | H360 May damage fertility or the unborn child H373 May cause damage to organs through prolonged or repeated exposure |
| Precautionary statement(s) | |
| Prevention | P201 Obtain special instructions before use. P202 Do not handle until all safety precautions have been read and understood. P280 Wear protective gloves/protective clothing/eye protection/face protection. P260 Do not breathe dust/fume/gas/mist/vapours/spray. |
| Response | P308+P313 IF exposed or concerned: Get medical advice/ attention. P314 Get medical advice/attention if you feel unwell. |
| Storage | P405 Store locked up. |
| Disposal | P501 Dispose of contents/container to ... |
2.3 Other hazards which do not result in classification
none
6. Other Information
- 6.0 Indications and Usage
- Sorafenib tosylate is a new type of multi-target antitumor drug, was developed by the German Bayer Pharmaceuticals, and displayed expansive antitumor activity in preclinical animal tests. Sorafenib tosylate is mainly used in advanced liver cancer treatment and is well tolerated.
- 6.1 Mechanisms of Action
- Sorafenib tosylate can simultaneously affect tumor cells and tumor blood vessels. It has a double antitumor effect: it can block the cell signal transduction pathways mediated by RAF/MEK/ERK to directly inhibit tumor cell growth, while also inhibiting VEGF and platelet derived growth factors (PDGF) receptors to prevent the formation of new tumor blood vessels, thus indirectly inhibiting tumor cell growth.
- 6.2 Clinical Research
- In a stage three randomized clinical study of American and European treatments for advanced kidney cancer, 903 cases advanced kidney patients who had experienced one unsuccessful systematic treatment (biological immunity or chemotherapy) were randomly split into two groups. One group received sorafenib tosylate, while the other received a placebo. Mid-term analysis found already 222 deaths and the objective efficacy of the two groups to be 10% and 2%, while 74% and 53% of patients had stabilized conditions. The sorafenib tosylate group’s survival period was longer than that of the placebo group, with the risk ratio as 0.72. However, this different does not have statistical significance, as this is only a mid-term analysis, and final analysis after treatment will yield the correct survival period comparison.
602 advanced liver cancer patients selected from the USA, Europe, Australia, and other countries and areas, who did not receive systematic treatment, were included in a study. Results showed that compared to the placebo, taking sorafenib tosylate could extend their total survival period of patients with late stage or primary liver cancer by about 44% and their extend disease progression period by about 73%. - View all
- 6.3 Adverse reactions
- Manageable diarrhea, rashes, fatigue, hand-foot syndrome, hypertension, alopecia, nausea, vomiting, and loss of appetite.
- 6.4 Uses
- Sorafenib Tosylate (Bay 43-9006, Nexavar) is a small molecular inhibitor of VEGFR, PDGFR, c-Raf and B-Raf with IC50s of 18 nM, 10 nM, 3 nM and 15 nM, respectively.
- 6.5 Uses
- Sorafenib Tosylate (Bay 43-9006) is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM, respectively
- 6.6 Uses
- An inhibitor of Flk-1 (VEGFR), PDGFR and Raf kinases.
- 6.7 Brand name
- Nexavar (Bayer).
- 6.8 General Description
- Sorafenib is available in 200-mg tablets for oral administrationand is used in the treatment of RCC and colon cancer.The agent is classified as a multikinase inhibitor because ofits action on numerous kinase enzymes including thePDGF-R, VEGF-R, Kit, and Raf. Sorafenib is 39% to 48% bioavailable and CYP3A4-mediated metabolism giveseight identified metabolites including the N-oxide, which isequally active with the parent. However, the majority of thedrug in plasma is present as the parent compound.Sorafenib is highly protein bound (99.5%). The drug iseliminated primarily in the feces (77%) with 19% appearingin the urine as glucuronides (UGT1A1) and has a eliminationhalf-life of 24 to 48 hours. The most commonly seentoxicity is skin rash that normally occurs within the first6 weeks of therapy. Other adverse effects include hypertension,fatigue, increased wound healing time, and increasedrisk of bleeding.
- 6.9 Description
- Sorafenib (475207-59-1) was initially developed as a Raf kinase inhibitor, IC50 = 6 nM, but has been shown to inhibit many receptor tyrosine kinases including BRAF (IC50 = 22 nM); VEGFR-2 (IC50 = 90 nM); VEGFR-3 (IC50 = 20 nM); PDGFR-β (IC50 = 57 nM); Flt3 (IC50 = 58 nM); c-KIT (IC50 = 68 nM); FGFR-1 (IC50 = 580 nM).1?Paradoxically more potent in a cellular assay (IC50 = 20 nM) compared to an isolated enzyme assay (IC50 = 107 nM) for c-Fms.2?Inhibits activation of MAPK pathway and ERK phosphorylation.3?Induces caspase-independent apoptosis in melanoma cells.4?Sorafenib is a clinically useful anticancer agent.
- 6.10 References
- 1) Wilhelm et al. (2004), 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., 64 7099 2) Guo et al. (2006), Inhibition of phosphorylation of the colony-stimulating factor-1 receptor (c-Fms) tyrosine kinase in transfected cells by ABT-869 and other tyrosine kinase inhibitors; Mol. Cancer Ther., 5 1007 3) Wilhelm et al. (2003), The novel Raf inhibitor BAY 43-9006 blocks signaling and proliferation in BRAF mutant and wildtype melanoma and colorectal tumor cell lies; Proc. Am. Assoc. Cancer Res., 44 106609 4) Panka et al. (2006), The Raf inhibitor BAY 43-9006 (Sorafenib) induces caspase-independent apoptosis in melanoma cells; Cancer Res., 66 1611
- 6.11 Mesh
- Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)|Agents that inhibit PROTEIN KINASES. (See all compounds classified as Protein Kinase Inhibitors.)
- 6.12 Mesh Entry Terms
- 4-(4-(3-(4-Chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2-carboxylic acid methyamide-4-methylbenzenesulfonate
- 6.13 Use Classification
- Human drugs -> Orphan -> Nexavar -> EMA Drug Category|Antineoplastic agents -> Human pharmacotherapeutic group|Human drugs -> Rare disease (orphan)|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients
7. Computational chemical data
- Molecular Weight: 637.02657g/mol
- Molecular Formula: C28H24ClF3N4O6S
- Compound Is Canonicalized: True
- XLogP3-AA: null
- Exact Mass: 636.1057179
- Monoisotopic Mass: 636.1057179
- Complexity: 853
- Rotatable Bond Count: 6
- Hydrogen Bond Donor Count: 4
- Hydrogen Bond Acceptor Count: 10
- Topological Polar Surface Area: 155
- Heavy Atom Count: 43
- Defined Atom Stereocenter Count: 0
- Undefined Atom Stereocenter Count: 0
- Defined Bond Stereocenter Count: 0
- Undefined Bond Stereocenter Count: 0
- Isotope Atom Count: 0
- Covalently-Bonded Unit Count: 2
- CACTVS Substructure Key Fingerprint: AAADceB7uYBEAAAAAAAAAAAAAAAAAAAAAAA8YMEAAAAAAAAB1AAAHwYQCAAADA7B3jQ/x5LIFIKoAzV3VHDCiGA3JyAI2Lm+btiMZnLFt7uWOSju1hvI6ae6yAAOEEBAQAABAAAggICAAAIAAAAAAAAAAA==
8. Question & Answer
-
Uses of Sorafenib Sorafenib is a chemotherapy drug used to treat kidney, liver, and thyroid cancer. It effectively slows or stops the growth of cancer cells. How to Use Sorafenib Tablet Prior to start..
9. Recommended Suppliers
-
- Products:Anastrozole,Letrozole,Epalrestat,Rhodanine-3-acetic acid,Methylboronic acid
- Tel:00-86-18616556591
- Email:nataling@vip.163.com
-
- Products:Medical intermediate
- Tel:86-359-3088066
- Email:yangmai@yabaoyaoye.com
-
- Products:We mainly export sles, labsa, glycerin, propylene glycol, castic soda, all kinds of plastic particles, fertilizer and other chemical products
- Tel:00-86-17731936018
- Email:alice@anrunchem.com
-
- Products:Plastic granules,chemical product
- Tel:+86-22-17622601053
- Email:mgmt@furuntongda.com
-
- Products:We are engaged in the development, marketing and sales of apis, intermediates, natural products (extracts), fine chemicals, food additives, agricultural chemicals and other products.
- Tel:0086-0319-19133911216
- Email:Jany1001@chengcaibio.com
10. Realated Product Infomation
skype
3YRS
