ChemicalBook--->CAS DataBase List--->417716-92-8

417716-92-8

417716-92-8 Structure

417716-92-8 Structure
IdentificationBack Directory
[Name]

4-[3-Chloro-4-(cyclopropylaminocarbonyl)aminophenoxy]-7-methoxy-6-quinolinecarboxamide
[CAS]

417716-92-8
[Synonyms]

E7080
ER-203492-00
E7080 (Lenvatinib)
Lenvatinib (E7080)
4-(3-chloro-4-(3-cyclopropylureido)phenoxy)-7-methoxyquinoline-6-carboxamide
1-(4-(6-carbamoyl-7-methoxyquinolin-4-yloxy)-2-chlorophenyl)-3-cyclopropylurea
4-[3-chloro-4-(cyclopropylcarbamoylamino)phenoxy]-7-methoxyquinoline-6-carboxamide
E70801-(4-(6-carbamoyl-7-methoxyquinolin-4-yloxy)-2-chlorophenyl)-3-cyclopropylurea
4-[3-Chloro-4-(cyclopropylaminocarbonyl)aminophenoxy]-7-methoxy-6-quinolinecarboxamide
4-[3-Chloro-4-(cyclopropylaminocarbonyl)aminophenoxy]-7-methoxy-6-quinolinecarboxamide XEN445
4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide methanesulfonate
[EINECS(EC#)]

1592732-453-0
[Molecular Formula]

C21H19ClN4O4
[MDL Number]

MFCD16038644
[MOL File]

417716-92-8.mol
[Molecular Weight]

426.85
Chemical PropertiesBack Directory
[Melting point ]

>216°C (dec.)
[Boiling point ]

627.2±55.0 °C(Predicted)
[density ]

1.46
[storage temp. ]

-20°C
[solubility ]

Soluble in DMSO (up to 20 mg/ml)
[form ]

solid
[pka]

13.09±0.70(Predicted)
[color ]

White
[Stability:]

Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
[CAS DataBase Reference]

417716-92-8
Hazard InformationBack Directory
[Uses]

E7080 (Lenvatinib) is a multi-target inhibitor of VEGFR2 and VEGFR3 with IC50 of 4 nM and 5.2 nM, respectively.
[Definition]

ChEBI: A member of the class of quinolines that is the carboxamide of 4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxylic acid. A multi-kinase inhibitor and orphan drug used (as its mesylate salt) for the treatment of various types of thyroid cancer that do not respond to radioiodine.
[Description]

Lenvatinib is an inhibitor of the receptor tyrosine kinases VEGF receptor 2 (VEGFR2) and VEGFR3 (IC50s = 4 and 5.2 nM, respectively). It also inhibits the related kinases VEGFR1, FGFR1, PDGFRα, PDGFRβ and Kit (IC50s = 22, 46, 51, 39, and 100 nM, respectively). Lenvatinib (30 mg/kg, twice per day) reduces tumor growth in an H146 small cell lung cancer mouse xenograft model and induces tumor regression when administered at a dose of 100 mg/kg twice per day. Formulations containing lenvatinib have been used in the treatment of differentiated thyroid cancer, renal cell carcinoma, and hepatocellular carcinoma.
[References]

1) Matsui et al. (2008), E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition; Int. J. Cancer, 122 664 2) Matsui et al. (2008), Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R)2 and VEGF-R3 kinase; Clin. Cancer Res., 14 5459 3) Glen et al. (2011), E7080, a multi-targeted tyrosine kinase inhibitor suppresses tumor cell migration and invasion; BMC Cancer, 11 309 4) Yamamoto et al. (2014), Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage; Vasc. Cell, 6 18
Questions And AnswerBack Directory
[Thyroid cancer drugs]

Lenvatinib is a thyroid cancer drug developed by Eisai Corporation of Japan (Code: E7080), belonging to the inhibitor of oral multi-receptor tyrosine kinase (RTK) and can inhibit the kinase activity of the vascular endothelial growth factor (VEGF) Receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib can also inhibit the involvement of other RTKs in pathological angiogenesis, tumor growth, and cancer progression except for their normal cellular functions including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; platelet-derived growth factor receptor (PDGFR [alpha]), KIT, and RET.
[Indications]: Lenvatinib is suitable for the treatment of patients of thyroid cancer of local recurrence or metastasis type, progressivity type and radioactive iodine-refractory differentiated type.
On February 13, 2015, the US FDA approved anticancer drug Lenvatinib for the treatment of thyroid cancer. Lenvatinib is a multi-target enzyme inhibitor, being capable of inhibiting the VEGFR2 and VEGFR3 (vascular endothelial growth factor receptor). The trade name of Lenvatinib is Lenvima.
On May 20, 2015, the European Medicines Agency (EMA) approved Lenvatinib for the treatment of invasive, locally advanced or metastatic differentiated (papillary, follicular, Hurthle type) thyroid cancer (DTC). In the trial, the median survival time for patients of radioactive iodine-refractory DTC treated with Lenvatinib was 18 months while the value for patients who take placebo is only 3 months.
In Europe, Lenvatinib will compete with Bayer's kinase inhibitor sorafenib (trade name: Nexavar), which had been respectively approved by EMA and the US Food and Drug Administration for the treatment of radioactive iodine refractory DTC in 2014 and 2013, respectively. At the time, Sorafenib had been reported to be the first targeted therapeutics to be marketed for the past 40 years in the treatment of refractory DTCs. The marketing applications of Lenvatinib in Switzerland, South Korea, Canada, Singapore, Russia, Australia and Brazil are also under review.
Information regarding the pharmacological effects, clinical evaluation, and indication of the thyroid cancer drug Lenvatinib were compiled and edited by Tongtong from Chemicalbook (2015-09-22).
[Biological activity]

Lenvatinib (E7080) is a multi-target inhibitor with the most potent effect on VEGFR2 (KDR)/VEGFR3 (Flt-4) with an IC50 of 4 nM/5.2 and weaker effect on VEGFR1/Flt-1. The selectivity of targeting on VEGFR 2/ 3 is about 10 times as high as that of targeting on FGFR1 and PDGFRα/β. Phase 3.
[In vitro study]

E7080 can effectively inhibit the angiogenesis, also significantly inhibit the VEGF/KDR and SCF/KIT signaling pathway. Based on the in vitro receptor tyrosine and serine/threonine kinase assays, the IC50 of E7080 in inhibiting Flt-1, KDR, and Flt-4 were 22, 4.0 and 5.2 nM, respectively. In addition to these kinases, E7080 can also inhibit FGFR1 and PDGFR tyrosine kinases, acting on FGFR1, PDGFRα and PDGFRβ with IC50 values of 46, 51 and 100 nM, respectively. When E7080 acted respectively on HUVECs stimulated by VEGF and VEGF-C, respectively, and effectively inhibit VEGFR2 and VEGFR3 phosphorylation with IC50 of 0.83 nM and 0.36 nM, respectively. Recent studies have shown that treatment with 1 μM and 10 μM and E7080, through inhibiting the FGFR and PDGFR signaling pathway, can significantly inhibit cell migration and invasion.
[In vivo studies]

Orally administration of E7080 at a dose of 30 mg/kg and 100 mg/kg for the treatment of H146 xenograft tumor model can inhibit the tumor growth in a dose-dependent manner. At 100 mg/kg, it can result in tumor regression. Moreover, treatment with a dose of 100 mg/kg of E7080, compared with the VEGF antibody and Imatinib treatment, can reduce the microvascular density more.
[Feature]

E7080 is an orally active multi-target kinase inhibitor.
Spectrum DetailBack Directory
[Spectrum Detail]

Lenvatinib(417716-92-8)1HNMR
417716-92-8 suppliers list
Company Name: Zison Pharmaceutical (Shandong) Co., Ltd.
Tel: +86-0086-531-88259693 +86-18660188356 , +86-18660188356
Website: http://www.zisonpharm.cn/
Company Name: Baoji Guokang Healthchem co.,ltd
Tel: +8615604608665 15604608665 , 15604608665
Website: www.gk-bio.com
Company Name: Senova Technology Co. Ltd.
Tel: +86-075586703119 +86-18503098836 , +86-18503098836
Website: http://www.senovatech.com/
Company Name: Zhengzhou Anhuida Chemical Co., Ltd
Tel: +8615903659408 , +8615903659408
Website: www.chemicalbook.com/ShowSupplierProductsList1000347/0.htm
Company Name: Capot Chemical Co.,Ltd.
Tel: 571-85586718 +8613336195806 , +8613336195806
Website: http://www.capotchem.com
Company Name: Beijing Cooperate Pharmaceutical Co.,Ltd
Tel: 010-60279497
Website: http://www.cooperate-pharm.com
Company Name: Shanghai Bojing Chemical Co.,Ltd.
Tel: +86-21-37122233 +86-13795318958 , +86-13795318958
Website: http://www.bj-chem.com
Company Name: Henan Tianfu Chemical Co.,Ltd.
Tel: +86-0371-55170693 +86-19937530512 , +86-19937530512
Website: https://www.tianfuchem.com/
Company Name: Hangzhou FandaChem Co.,Ltd.
Tel: +8615858145714 , +8615858145714
Website: http://www.fandachem.com
Company Name: Guangzhou PI PI Biotech Inc
Tel: +86-020-81716320 +86-18371201331 , +86-18371201331
Website: http://www.pipitech.com/
Company Name: Nanjing ChemLin Chemical Industry Co., Ltd.
Tel: 025-83697070
Website: www.echemlin.cn
Company Name: Shanghai Yingrui Biopharma Co., Ltd.
Tel: +86-21-33585366 E-mail:sales03@shyrchem.com
Website: www.shyrchem.com
Company Name: ATK CHEMICAL COMPANY LIMITED
Tel: 21-51619050
Website: http://www.atkchemical.com
Company Name: Anqing Chico Pharmaceutical Co., Ltd.
Tel: 15380796838
Website: www.chemicalbook.com/ShowSupplierProductsList30721/0.htm
Company Name: Lianyungang happen teng technology co., LTD
Tel: 15950718863
Website: www.chemicalbook.com/ShowSupplierProductsList30820/0.htm
Company Name: career henan chemical co
Tel: +86-0371-86658258
Website: www.coreychem.com/index.html
Company Name: Zhejiang ZETian Fine Chemicals Co. LTD
Tel: 18957127338 , 18957127338
Website: http://www.zetchem.com/
Company Name: TianYuan Pharmaceutical CO.,LTD
Tel: +86-755-23284190 13684996853
Website: www.tianpharm.com
Tags:417716-92-8 Related Product Information
159351-69-6 319460-85-0 849217-68-1 1110813-31-4 571190-30-2 871700-17-3 477600-75-2 52671-64-4 656247-17-5 943319-70-8 1454846-35-5 857890-39-2 1788901-86-9 1257628-77-5 205448-65-3 205448-66-4 17609-80-2 417721-36-9