Lenvatinib Mesylate

Names

[ Name ]:
Lenvatinib Mesylate

[Synonym ]:
4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide mesylate
Lenvatinib mesilate
lenvatinib mesylate
Lenvatinib mesylate [USAN]
4-{3-Chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxy-6-quinolinecarboxamide methanesulfonate (1:1)
4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide methanesulfonate
4-[3-chloro-4-(cyclopropylcarbamoylamino)phenoxy]-7-methoxyquinoline-6-carboxamide,methanesulfonic acid
6-Quinolinecarboxamide, 4-[3-chloro-4-[[(cyclopropylamino)carbonyl]amino]phenoxy]-7-methoxy-, methanesulfonate (1:1)
Lenvatinib mesilate (JAN)
lenvatinib methanesulfonate
UNII-3J78384F61

Biological Activity

[Description]:

Lenvatinib mesylate (E7080 mesylate), an oral, multi-targeted tyrosine kinase inhibitor that inhibits VEGFR1-3, FGFR1-4, PDGFR, KIT, and RET, shows potent antitumor activities[1][2].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> PDGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> VEGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> c-Kit

[Target]

VEGFR1:22 nM (IC50)

VEGFR2:4 nM (IC50)

VEGFR3:5.2 nM (IC50)

FGFR1:46 nM (IC50)

FGFR2

FGFR3

FGFR4

PDGFRα:51 nM (IC50)

PDGFRβ:39 nM (IC50)

c-Kit:100 nM (IC50)

RET

[In Vitro]

Lenvatinib mesylate (E7080 mesylate) has IC50s of 4, 5.2, 22 nM for VEGFR2(KDR), VEGFR3(Flt-4), and VEGFR1/Flt-1, respectively. Lenvatinib inhibits PDGFRα, PDGFRβ, FGFR1, and KIT with IC50s of 51, 39, 46, 100 nM, respectively[3].

[In Vivo]

Lenvatinib mesylate (E7080 mesylate) (100 mg/kg, p.o.) is administeredand bevacizumab significantly inhibits local tumor growth at the m.f.p., and at the end of treatment, Lenvatinib mesylate also significantly inhibits metastasis to both regional lymph nodes and distant lung[3]. Lenvatinib mesylate (E7080 mesylate) inhibits the growth of H146 tumor at 30 and 100 mg/kg (BID, QDx21) in a dose-dependent manner and causes tumor regression at 100 mg/kg in H146 xenograft model. IHC analysis with anti-CD31 antibody shows that lenvatinib at 100 mg/kg decreases microvessel density more than anti-VEGF antibody and imatinib treatment[4].

[References]

[1]. Kudo M, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellularcarcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173.

[2]. Suyama K, et al. Lenvatinib: A Promising Molecular Targeted Agent for Multiple Cancers. Cancer Control. 2018 Jan-Dec;25(1):1073274818789361.

[3]. 3.Matsui J, et al. 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. 2008, 14(17),545.

[4]. Matsui J, et al. 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. 2008, 122(3), 664-671.