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Details

Stereochemistry ACHIRAL
Molecular Formula C21H19ClN4O4
Molecular Weight 426.853
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LENVATINIB

SMILES

COC1=C(C=C2C(OC3=CC=C(NC(=O)NC4CC4)C(Cl)=C3)=CC=NC2=C1)C(N)=O

InChI

InChIKey=WOSKHXYHFSIKNG-UHFFFAOYSA-N
InChI=1S/C21H19ClN4O4/c1-29-19-10-17-13(9-14(19)20(23)27)18(6-7-24-17)30-12-4-5-16(15(22)8-12)26-21(28)25-11-2-3-11/h4-11H,2-3H2,1H3,(H2,23,27)(H2,25,26,28)

HIDE SMILES / InChI

Molecular Formula C21H19ClN4O4
Molecular Weight 426.853
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Lenvatinib, developed by Eisai Co., is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. These receptor tyrosine kinases (RTKs) located in the cell membrane play a central role in the activation of signal transduction pathways involved in the normal regulation of cellular processes, such as cell proliferation, migration, apoptosis and differentiation, and in pathogenic angiogenesis, lymphogenesis, tumour growth and cancer progression. In particular, VEGF has been identified as a crucial regulator of both physiologic and pathologic angiogenesis and increased expression of VEGF is associated with a poor prognosis in many types of cancers. Lenvatinib is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer. Most patients with thyroid cancer have a very good prognosis with treatment (98% 5 year survival rate) involving surgery and hormone therapy. However, for patients with RAI-refractory thyroid cancer, treatment options are limited and the prognosis is poor, leading to a push for the development of more targeted therapies such as lenvatinib. Lenvatinib is marketed under the trade name Lenvima, it is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer.

CNS Activity

Originator

Approval Year

TargetsConditions
PubMed

PubMed

TitleDatePubMed
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.
2008 Feb 1
E7080, a multi-tyrosine kinase inhibitor, suppresses the progression of malignant pleural mesothelioma with different proangiogenic cytokine production profiles.
2009 Dec 1
A model of hypertension and proteinuria in cancer patients treated with the anti-angiogenic drug E7080.
2010 Aug
Antitumour activity of oral E7080, a novel inhibitor of multiple tyrosine kinases, in human sarcoma xenografts.
2011 Aug 1
E7080, a multi-targeted tyrosine kinase inhibitor suppresses tumor cell migration and invasion.
2011 Jul 22
Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.
2012 Dec 27
Lenvatinib: first global approval.
2015 Apr
Neuroendocrine cancer: SELECT—lenvatinib in thyroid cancer.
2015 Apr
Patents

Sample Use Guides

In Vivo Use Guide
Recommended Dose for DTC The recommended daily dose of LENVIMA (Lenvatinib) is 24 mg (two 10 mg capsules and one 4 mg capsule) orally taken once daily with or without food. Continue LENVIMA until disease progression or until unacceptable toxicity. Take LENVIMA at the same time each day. If a dose is missed and cannot be taken within 12 hours, skip that dose and take the next dose at the usual time of administration. Recommended Dose for RCC The recommended daily dose of LENVIMA (Lenvatinib) is 18 mg (one 10 mg capsule and two 4 mg capsules) in combination with 5 mg everolimus orally taken once daily with or without food
Route of Administration: Oral
In Vitro Use Guide
Lenvatinib inhibited VEGF induced proliferation and tube formation of HUVECs with IC50 values of 3.4 and 2.7 nM, respectively
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:44:25 UTC 2019
Edited
by admin
on Mon Oct 21 20:44:25 UTC 2019
Record UNII
EE083865G2
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LENVATINIB
DASH   INN   MI   USAN   WHO-DD  
USAN   INN  
Official Name English
4-(3-CHLORO-4-((CYCLOPROPYLAMINOCARBONYL)AMINO)PHENOXY)-7-METHOXY-6-QUINOLINECARBOXAMIDE
Systematic Name English
6-QUINOLINECARBOXAMIDE, 4-(3-CHLORO-4-(((CYCLOPROPYLAMINO)CARBONYL)AMINO)PHENOXY)-7-METHOXY-
Systematic Name English
LENVATINIB [INN]
Common Name English
ER-203492-00
Code English
LENVATINIB [WHO-DD]
Common Name English
E-7080
Code English
LENVATINIB [MI]
Common Name English
LENVATINIB [USAN]
Common Name English
6-QUINOLINECARBOXAMIDE, 4-(3-CHLORO-4-(((CYCLOPROPYLAMINO)CARBONYL)AMINO)PHENOXY)- 7-METHOXY-
Systematic Name English
E7080
Code English
4-(3-CHLORO-4-((CYCLOPROPYLCARBAMOYL)AMINO)PHENOXY)-7-METHOXYQUINOLINE-6-CARBOXAMIDE
Systematic Name English
N-(4-((6-CARBAMOYL-7-METHOXYQUINOLIN-4-YL)OXY)-2-CHLOROPHENYL)-N'-CYCLOPROPYLUREA
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
FDA ORPHAN DRUG 423614
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
NCI_THESAURUS C93259
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
WHO-ATC L01XE29
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
FDA ORPHAN DRUG 378412
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
NDF-RT N0000175605
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
FDA ORPHAN DRUG 423714
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
EU-Orphan Drug EU/3/15/1460
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
Code System Code Type Description
LactMed
417716-92-8
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
PRIMARY
CAS
417716-92-8
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
PRIMARY
INN
9361
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
PRIMARY
ChEMBL
CHEMBL1289601
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
PRIMARY
MERCK INDEX
M6764
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
PRIMARY Merck Index
WIKIPEDIA
LENVATINIB
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
PRIMARY
DRUG BANK
DB09078
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
PRIMARY
IUPHAR
7426
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
PRIMARY
RXCUI
1603296
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
PRIMARY RxNorm
EVMPD
SUB64419
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
PRIMARY
NCI_THESAURUS
C95124
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
PRIMARY
NDF-RT
N0000020000
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
PRIMARY Receptor Tyrosine Kinase Inhibitors [MoA]
EPA CompTox
417716-92-8
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
PRIMARY
PUBCHEM
9823820
Created by admin on Mon Oct 21 20:44:25 UTC 2019 , Edited by admin on Mon Oct 21 20:44:25 UTC 2019
PRIMARY
Related Record Type Details
BINDER->LIGAND
BINDING
INHIBITOR -> METABOLIC ENZYME
INHIBITOR
PLASMA
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
INHIBITOR -> METABOLIC ENZYME
Time-dependent inhibition. significant effect with other drugs which are substrate of CYP3A4 at clinical dose of Lenvatinib
MAJOR
PLASMA
Related Record Type Details
METABOLITE LESS ACTIVE -> PARENT
MAJOR
PLASMA
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC