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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=CC2=C(C=C1C(N)=O)C(OC3=CC=C(NC(=O)NC4CC4)C(Cl)=C3)=CC=N2

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
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
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

Targets

Primary TargetPharmacologyConditionPotency
4.0 nM [IC50]
5.2 nM [IC50]
22.0 nM [IC50]
39.0 nM [IC50]
8.2 nM [Ki]
22.0 nM [Ki]
15.0 nM [Ki]
11.0 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
LENVIMA
Primary
LENVIMA

Cmax

ValueDoseCo-administeredAnalytePopulation
325 ng/mL
2 mg single, oral
LENVATINIB plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
3010 ng × h/mL
2 mg single, oral
LENVATINIB plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
28 h
2 mg single, oral
LENVATINIB plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
1.5%
LENVATINIB plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

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
Record UNII
EE083865G2
Record Status Validated (UNII)
Record Version