LENVATINIB

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 Search

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	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.drugbank.ca/drugs/DB09078
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206947s003lbl.pdf

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

Targets

Primary Target	Pharmacology	Potency
Vascular endothelial growth factor receptor 2 112 Target ID: CHEMBL279 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206947s003lbl.pdf	Antagonist 2849	4.0 nM [IC50]
Vascular endothelial growth factor receptor 3 41 Target ID: CHEMBL1955 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206947s003lbl.pdf	Antagonist 2849	5.2 nM [IC50]
Vascular endothelial growth factor receptor 1 44 Target ID: CHEMBL1868 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206947s003lbl.pdf	Antagonist 2849	22.0 nM [IC50]
Platelet-derived growth factor receptor beta 56 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17943726	Antagonist 2849	39.0 nM [IC50]
Fibroblast growth factor receptor 2 25 Target ID: CHEMBL4142 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25197551	Antagonist 2849	8.2 nM [Ki]
Fibroblast growth factor receptor 1 46 Target ID: CHEMBL3650 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25197551	Antagonist 2849	22.0 nM [Ki]
Fibroblast growth factor receptor 3 32 Target ID: CHEMBL2742 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25197551	Antagonist 2849	15.0 nM [Ki]
Stem cell growth factor receptor 57 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25197551	Antagonist 2849	11.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Differentiated thyroid cancer 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206947s003lbl.pdf	Primary		Approved 8583	LENVIMA Approved Use LENVIMA is a kinase inhibitor that is indicated for: • Differentiated Thyroid Cancer (DTC): single agent for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC. • Renal Cell Cancer (RCC): in combination with everolimus, for patients with advanced RCC following one prior anti-angiogenic therapy. Launch Date 2015
Renal cell cancer 7 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206947s003lbl.pdf	Primary		Approved 8583	LENVIMA Approved Use LENVIMA is a kinase inhibitor that is indicated for: • Differentiated Thyroid Cancer (DTC): single agent for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC. • Renal Cell Cancer (RCC): in combination with everolimus, for patients with advanced RCC following one prior anti-angiogenic therapy. Launch Date 2015

C_max

Value	Dose	Co-administered	Analyte	Population
325 ng/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/lenvima-epar-public-assessment-report_en.pdf	24 mg single, oral dose: 24 mg route of administration: Oral experiment type: SINGLE co-administered:		LENVATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
3010 ng × h/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/lenvima-epar-public-assessment-report_en.pdf	24 mg single, oral dose: 24 mg route of administration: Oral experiment type: SINGLE co-administered:		LENVATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
28 h OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/lenvima-epar-public-assessment-report_en.pdf	24 mg single, oral dose: 24 mg route of administration: Oral experiment type: SINGLE co-administered:		LENVATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206947s007lbl.pdf			LENVATINIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
32 mg 1 times / day steady, oral Highest studied dose Dose: 32 mg, 1 times / day Route: oral Route: steady Dose: 32 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22516948	unhealthy, 54 years (range 25–84 years) Health Status: unhealthy Age Group: 54 years (range 25–84 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22516948	DLT: Proteinuria... Other AEs: Hypertension, Nausea... Dose limiting toxicities: Proteinuria (grade 3, 2 patients) Other AEs: Hypertension (57%) Nausea (43%) Diarrhoea (57%) Stomatitis (57%) Proteinuria (43%) Vomiting (14%) Lethargy (29%) Dysphonia (43%) Dry skin (14%) Fatigue (14%) Anorexia (29%) Constipation (14%) Headache (29%) Sources: https://pubmed.ncbi.nlm.nih.gov/22516948
25 mg 1 times / day steady, oral MTD Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22516948	unhealthy, 54 years (range 25–84 years) Health Status: unhealthy Age Group: 54 years (range 25–84 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22516948	Other AEs: Hypertension, Nausea... Other AEs: Hypertension (63%) Nausea (58%) Diarrhoea (50%) Stomatitis (63%) Proteinuria (29%) Vomiting (33%) Lethargy (38%) Dysphonia (46%) Dry skin (46%) Fatigue (21%) Anorexia (21%) Constipation (33%) Headache (29%) Abdominal pain (29%) Sources: https://pubmed.ncbi.nlm.nih.gov/22516948
12.5 mg 1 times / day steady, oral Dose: 12.5 mg, 1 times / day Route: oral Route: steady Dose: 12.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22516948	unhealthy, 54 years (range 25–84 years) Health Status: unhealthy Age Group: 54 years (range 25–84 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22516948	DLT: Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/22516948
16 mg 1 times / day steady, oral Dose: 16 mg, 1 times / day Route: oral Route: steady Dose: 16 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22516948	unhealthy, 54 years (range 25–84 years) Health Status: unhealthy Age Group: 54 years (range 25–84 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22516948	DLT: Hypertension, Fatigue... Dose limiting toxicities: Hypertension (grade 3, 1 patient) Fatigue (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/22516948
6.4 mg 1 times / day steady, oral Dose: 6.4 mg, 1 times / day Route: oral Route: steady Dose: 6.4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22516948	unhealthy, 54 years (range 25–84 years) Health Status: unhealthy Age Group: 54 years (range 25–84 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22516948	DLT: Febrile neutropenia... Dose limiting toxicities: Febrile neutropenia (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/22516948
24 mg 1 times / day steady, oral Recommended Dose: 24 mg, 1 times / day Route: oral Route: steady Dose: 24 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206947s000lbl.pdf	unhealthy, 64 years Health Status: unhealthy Age Group: 64 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206947s000lbl.pdf	Disc. AE: Hypertension, Asthenia... AEs leading to discontinuation/dose reduction: Hypertension (1.15%) Asthenia (1.15%) Hypertension (13%) Proteinuria (11%) Decreased appetite (10%) Diarrhea (10%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206947s000lbl.pdf
24 mg 1 times / day steady, oral Recommended Dose: 24 mg, 1 times / day Route: oral Route: steady Dose: 24 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206947Orig1s000MedR.pdf	unhealthy, 64 years Health Status: unhealthy Age Group: 64 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206947Orig1s000MedR.pdf	Disc. AE: Proteinuria, Renal failure acute... AEs leading to discontinuation/dose reduction: Proteinuria (0.77%) Renal failure acute (0.77%) Sepsis (0.77%) Abdominal pain upper (0.38%) Accidental overdose (0.38%) Acute myocardial infarction (0.38%) Acute respiratory failure (0.38%) Ataxia (0.38%) Blood alkaline phosphatase increased (0.38%) Cardio-respiratory arrest (0.38%) Cerebral microangiopathy (0.38%) Dizziness (0.38%) Epilepsy (0.38%) QT interval prolonged (0.38%) Fatigue (0.38%) Glossitis (0.38%) Hemorrhagic stroke (0.38%) Hyponatremia (0.38%) Laryngeal necrosis (0.38%) Memory impairment (0.38%) Myalgia (0.38%) Myocardial infarction (0.38%) Oropharyngeal pain (0.38%) Pneumonia (0.38%) Pulmonary embolism (0.38%) Sciatica (0.38%) Skin ulcer (0.38%) Spinal cord compression (0.38%) Stomatitis (0.38%) Vascular pseudoaneurysm (0.38%) Weight decreased (14.6%) Nausea (14.2%) Palmar-plantar erythrodysesthesia syndrome (12.3%) Asthenia (10.3%) Fatigue (9.9%) Stomatitis (8.8%) Vomiting (8%) Headache (5.4%) Arthralgia (5%) Abdominal pain (3.8%) Dehydration (3.5%) Myalgia (3%) Pneumonia (3%) Dysphonia (2.7%) Thrombocytopenia (2.7%) Dizziness (2.3%) Dysgeusia (2.3%) Dyspepsia (2.3%) Dysphagia (2.3%) Edema peripheral (2.3%) Oropharyngeal pain (2.3%) Platelet count decreased (2.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206947Orig1s000MedR.pdf
40 mg single, oral Highest studied dose Dose: 40 mg Route: oral Route: single Dose: 40 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206947s000lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206947s000lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206947s000lbl.pdf

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:85994	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:85994
ChemicalBook	CB12484883	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB12484883
eMolecules	31507658	https://www.emolecules.com/cgi-bin/more?vid=31507658
MolPort	MolPort-009-679-469	https://www.molport.com/shop/molecule-link/MolPort-009-679-469
Selleck Chemicals	E7080	http://www.selleckchem.com/products/E7080.html
ZINC	ZINC000003816292	http://zinc15.docking.org/substances/ZINC000003816292

PubMed

Title	Date	PubMed
Lenvatinib: first global approval.	2015-04	25795101
Neuroendocrine cancer: SELECT—lenvatinib in thyroid cancer.	2015-04	25707627
Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.	2012-12-27	23098265
Antitumour activity of oral E7080, a novel inhibitor of multiple tyrosine kinases, in human sarcoma xenografts.	2011-08-01	21225632
E7080, a multi-targeted tyrosine kinase inhibitor suppresses tumor cell migration and invasion.	2011-07-22	21781317
A model of hypertension and proteinuria in cancer patients treated with the anti-angiogenic drug E7080.	2010-08	20652729
E7080, a multi-tyrosine kinase inhibitor, suppresses the progression of malignant pleural mesothelioma with different proangiogenic cytokine production profiles.	2009-12-01	19934291
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.	2008-02-01	17943726

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 Mar 31 18:09:15 GMT 2025` Edited by `admin` on `Mon Mar 31 18:09:15 GMT 2025`
Record UNII	EE083865G2
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

lenvatinib [INN]

Preferred Name

English

LENVATINIB

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

ER-203492-00

Code

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

Lenvatinib [WHO-DD]

Common 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