Sorafenib Tosylate

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 · Sorafenib (Nexavar) · Sorafenib TsOH salt · Sorafenib 475207-59-1

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

식별자 및 물리적 특성

CAS No.	475207-59-1
분자식	C28H24ClF3N4O6S
평균 분자량	637 g/mol
단동위원소 질량	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

화학 및 물리적 성질

극성 표면적	155
수소 결합 공여자 수	4
수소 결합 수용자 수	10
회전 가능 결합 수	6
무거운 원자 수	43
형식 전하	0
복잡도	853
Human Drugs	Breast FeedingLactationAntineoplastic AgentsEnzyme InhibitorsProtein Kinase InhibitorsSignal Transduction InhibitorsTyrosine Kinase InhibitorsFDA approved drugs -> Active ingredientEMA approved medicines: Human medicine
녹는점	229-232°C
저장 조건	2-8°C(protect from light)
용해도	DMSO(최대 200mg/ml) 또는 에탄올(최대 3mg/ml)에 용해됩니다.
물리적 상태	고체
색상	회백색
안정성	제공된 대로 구매일로부터 2년 동안 안정적입니다. DMSO 또는 에탄올 용액은 -20°에서 최대 1개월 동안 보관할 수 있습니다.
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

안전 및 규제

GHS 분류	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)
건강 영향	Hand-foot skin reaction and rash represent the most common adverse reactionsmay increase the risk of bleeding (L1712)
노출 경로	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.
독성 요약	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

용도

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.

일반 설명

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.