ソラフェニブトシル酸塩

ソラフェニブトシル酸塩 · ソラフェニブトシル酸塩 (JAN) · トシル酸ソラフェニブ · 4-Methyl-3-((4-(3-pyridinyl)-2-pyrimidinyl)amino)-N-(5-(4-methyl-1H-imidazol-1-yl)-3-(trifluoromethyl)phenyl)benzamide monomethanesulfonate · CL050 · Sorafenib &Sorafeni tosylate · SORAFENIB TOSYLATE · Sorafinib mesylate

https://huagongshe.com/ja/chemical/406563

識別子と物理属性

CAS No.	475207-59-1
分子式	C28H24ClF3N4O6S
平均分子量	637 g/mol
単同位体質量	636.10571783 g/mol
SMILES	CNC(=O)c1cc(Oc2ccc(NC(=O)Nc3ccc(Cl)c(C(F)(F)F)c3)cc2)ccn1.Cc1ccc(S(=O)(=O)O)cc1
InChIKey	IVDHYUQIDRJSTI-UHFFFAOYSA-N
PubChem CID	406563
ChEMBL	CHEMBL1200485
ChEBI	CHEBI:50928
EC No.	641-758-8
DTXSID	DTXSID9047839
現地名	ソラフェニブトシル酸塩

化学・物理的性質

極性表面積	155
水素結合供与体数	4
水素結合受容体数	10
回転可能結合数	6
重原子数	43
形式電荷	0
複雑度	853
Human Drugs	Breast FeedingLactationAntineoplastic AgentsEnzyme InhibitorsProtein Kinase InhibitorsSignal Transduction InhibitorsTyrosine Kinase InhibitorsFDA approved drugs -> Active ingredientEMA approved medicines: Human medicine
融点	229-232°C
貯蔵条件	2-8°C(protect from light)
溶解度	DMSO (最大 200mg/ml) またはエタノール (最大 3mg/ml) に可溶。
外観・状態	個体
色	オフホワイト
安定性	購入日から2年間安定です。この DMSO またはエタノール溶液は、-20°C で 1 か月間保存できます。
InChIKey	IVDHYUQIDRJSTI-UHFFFAOYSA-N
SMILES	S(C1C=CC(C)=CC=1)(O)(=O)=O.O(C1C=CC(NC(=O)NC2C=CC(Cl)=C(C(F)(F)F)C=2)=CC=1)C1=CC=NC(C(=O)NC)=C1
CAS データベース	475207-59-1(CAS DataBase Reference)

安全性と法規制

GHS 分類	DangerH302 (31%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P260, P261, P264, P270, P271, P273, P280, P301+P317, P304+P340, P317, P318, P319, P330, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 42 reports by companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Hazard Classes and Categories	Acute Tox. 4 (31%)
Treatment	There is no specific treatment for NEXAVAR (Sorafenib ) overdose. (L1712)
健康影響	Hand-foot skin reaction and rash represent the most common adverse reactionsmay increase the risk of bleeding (L1712)
暴露経路	The mean relative bioavailability is 38-49% for the tablet form, when compared to an oral solution. Sorafenib reached peak plasma levels in 3 hours following oral administration. With a high-fat meal, bioavailability is reduced by 29% compared to administration in the fasted state.
毒性の概要	Sorafenib interacts with multiple intracellular (CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-&szlig). Several of these kinases are thought to be involved in angiogenesis, thus sorafenib reduces blood flow to the tumor. Sorafenib is unique in targeting the Raf/Mek/Erk pathway. By inhibiting these kinases, genetic transcription involving cell proliferation and angiogenesis is inhibited.
Signs and Symptoms	The highest dose of sorafenib studied clinically is 800 mg twice daily. The adverse reactions observed at this dose were primarily diarrhea and dermatologic events. No information is available on symptoms of acute overdose in animals because of the saturation of absorption in oral acute toxicity studies conducted in animals.
Carcinogen Classification	No indication of carcinogenicity to humans (not listed by IARC).
Drug Induced Liver Injury	Drug Induced Liver Injury Rank (DILIrank 2.0)Sorafenib tosylatevMost-DILI-concern8Warnings & precautionsDOI:10.1016/j.drudis.2016.02.015

用途

使用

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.

一般的な説明

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.