J u m p t o c o n t e n t
M a i n m e n u
M a i n m e n u
N a v i g a t i o n
● M a i n p a g e ● C o n t e n t s ● C u r r e n t e v e n t s ● R a n d o m a r t i c l e ● A b o u t W i k i p e d i a ● C o n t a c t u s ● D o n a t e
C o n t r i b u t e
● H e l p ● L e a r n t o e d i t ● C o m m u n i t y p o r t a l ● R e c e n t c h a n g e s ● U p l o a d f i l e
S e a r c h
Search
A p p e a r a n c e
● C r e a t e a c c o u n t ● L o g i n
P e r s o n a l t o o l s
● C r e a t e a c c o u n t ● L o g i n
P a g e s f o r l o g g e d o u t e d i t o r s l e a r n m o r e ● C o n t r i b u t i o n s ● T a l k
( T o p )
1 M e d i c a l u s e s
2 A d v e r s e e f f e c t s
3 I n t e r a c t i o n s
4 P h a r m a c o l o g y
T o g g l e P h a r m a c o l o g y s u b s e c t i o n
4 . 1 M e c h a n i s m o f a c t i o n
4 . 2 P h a r m a c o k i n e t i c s
5 C h e m i s t r y
6 H i s t o r y
7 R e f e r e n c e s
T o g g l e t h e t a b l e o f c o n t e n t s
L e n v a t i n i b
1 0 l a n g u a g e s
● ا ل ع ر ب ي ة ● D e u t s c h ● E s p a ñ o l ● ف ا ر س ی ● F r a n ç a i s ● 日 本 語 ● ଓ ଡ ଼ ି ଆ ● P o r t u g u ê s ● С р п с к и / s r p s k i ● S r p s k o h r v a t s k i / с р п с к о х р в а т с к и
E d i t l i n k s
● A r t i c l e ● T a l k
E n g l i s h
● R e a d ● E d i t ● V i e w h i s t o r y
T o o l s
T o o l s
A c t i o n s
● R e a d ● E d i t ● V i e w h i s t o r y
G e n e r a l
● W h a t l i n k s h e r e ● R e l a t e d c h a n g e s ● U p l o a d f i l e ● S p e c i a l p a g e s ● P e r m a n e n t l i n k ● P a g e i n f o r m a t i o n ● C i t e t h i s p a g e ● G e t s h o r t e n e d U R L ● D o w n l o a d Q R c o d e ● W i k i d a t a i t e m
P r i n t / e x p o r t
● D o w n l o a d a s P D F ● P r i n t a b l e v e r s i o n
I n o t h e r p r o j e c t s
● W i k i m e d i a C o m m o n s
A p p e a r a n c e
F r o m W i k i p e d i a , t h e f r e e e n c y c l o p e d i a
Lenvatinib Trade names Lenvima, others Other names E7080 AHFS /Drugs.com Monograph License data
Pregnancy
Routes of By mouth ATC code Legal status
AU S4 (Prescription only)[1]
CA ℞-only [2]
US ℞-only
EU [3]
Bioavailability 85% (estimated) Protein binding 98–99% Metabolism CYP3A4 , aldehyde oxidase , non-enzymaticMetabolites Desmethyl-lenvatinib (M2) and others Elimination half-life 28 hours Excretion ~65% feces , 25% urine
4-[3-Chloro-4-(cyclopropylcarbamoylamino)phenoxy]-7-methoxy-quinoline-6-carboxamide
CAS Number PubChem CID IUPHAR/BPS DrugBank ChemSpider UNII KEGG
as salt: D09920 N
ChEBI ChEMBL CompTox Dashboard (EPA ) Formula C 21 H 19 Cl N 4 O 4 Molar mass −1 3D model (JSmol )
C4CC4NC(=O)Nc3ccc(cc3Cl)Oc1ccnc(cc2OC)c1cc2C(=O)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) Y
Key:WOSKHXYHFSIKNG-UHFFFAOYSA-N Y
N Y (what is this?) (verify)
Lenvatinib , sold under the brand name Lenvima among others, is an anti-cancer medication for the treatment of certain kinds of thyroid cancer and for other cancers as well. It was developed by Eisai Co. and acts as a multiple kinase inhibitor against the VEGFR1 , VEGFR2 and VEGFR3 kinases.[4]
Medical uses [ edit ]
Lenvatinib is approved (since 2015) for the treatment of differentiated thyroid cancer that is either locally recurrent or metastatic , progressive, and did not respond to treatment with radioactive iodine (radioiodine).[5] [6]
In May 2016, the US Food and Drug Administration (FDA) approved it (in combination with everolimus ) for the treatment of advanced renal cell carcinoma following one prior anti-angiogenic therapy.[7]
The drug is also approved in the US and in the European Union for hepatocellular carcinoma that cannot be removed surgically in patients who have not received cancer therapy by mouth or injection.[8] [9]
Adverse effects [ edit ]
Hypertension (high blood pressure) was the most common side effect in studies (73% of patients, versus 16% in the placebo group), followed by diarrhoea (67% vs. 17%) and fatigue (67% vs. 35%).[6] hypotension (low blood pressure), thrombocytopenia (low blood platelet count), nausea, muscle and bone pain.[5]
Interactions [ edit ]
As lenvatinib moderately prolongs QT time , addition of other drugs with this property could increase the risk of a type of abnormal heart rhythm, namely torsades de pointes . No relevant interactions with enzyme inhibitors and inducers are expected.[6]
Pharmacology [ edit ]
Mechanism of action [ edit ]
Lenvatinib acts as a multiple kinase inhibitor . It inhibits the three main vascular endothelial growth factor receptors VEGFR1, 2 and 3, as well as fibroblast growth factor receptors (FGFR) 1, 2, 3 and 4, platelet-derived growth factor receptor (PDGFR) alpha, c-Kit , and the RET proto-oncogene . Some of these proteins play roles in cancerogenic signalling pathways . VEGFR2 inhibition is thought to be the main reason for the most common side effect, hypertension.[5]
Pharmacokinetics [ edit ]
Lenvatinib is absorbed quickly from the gut, reaching peak blood plasma concentrations after one to four hours (three to seven hours if taken with food). Bioavailability is estimated to be about 85%. The substance is almost completely (98–99%) bound to plasma proteins , mainly albumin .[5]
Lenvatinib is oxidized by cytochrome P450 enzymes (CYP), and further metabolized to the quinolinones M2' and M3' by aldehyde oxidase (AO ).[10]
Lenvatinib is metabolized by the liver enzyme CYP3A4 to desmethyl-lenvatinib (M2). M2 and lenvatinib itself are oxidized by aldehyde oxidase (AO ) to substances called M2' and M3',[10] N [5]
Terminal half-life is 28 hours, with about two thirds being excreted via the feces, and one quarter via the urine.[5]
Chemistry [ edit ]
Lenvatinib is used in form of the mesylate salt (CAS number 857890-39-2 ).
History [ edit ]
A phase I clinical trial in cancer patients was performed in 2006.[11] [12]
Lenvatinib was granted orphan drug status for treatment of various types of thyroid cancer that do not respond to radioiodine in the US and Japan in 2012 and in Europe in 2013.[13]
In February 2015, the U.S. FDA approved lenvatinib for treatment of progressive, radioiodine refractory differentiated thyroid cancer.[14] European Medicines Agency (EMA) approved the drug for the same indication.[15]
In May 2016, the FDA approved it (in combination with everolimus ) for the treatment of advanced renal cell carcinoma following one prior anti-angiogenic therapy.[7]
In August 2018, the FDA approved lenvatinib for the first-line treatment of people with unresectable hepatocellular carcinoma (HCC).[9]
References [ edit ]
^ "Kisplyx EPAR" . European Medicines Agency . 25 August 2016. Retrieved 7 January 2024 .
^ Matsui J, Funahashi Y, Uenaka T, Watanabe T, Tsuruoka A, Asada M (September 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" . Clinical Cancer Research . 14 17 ): 5459–65. doi :10.1158/1078-0432.CCR-07-5270 PMID 18765537 .
^ a b c d e f Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
^ a b c FDA Professional Drug Information
^ a b "Lenvatinib in combination with Everolimus" . U.S. Food and Drug Administration (FDA) . 16 May 2016.
^ "Lenvima" . European Medicines Agency . 2015-05-28.
^ a b "FDA approves lenvatinib for unresectable hepatocellular carcinoma" . U.S. Food and Drug Administration (FDA) . 16 August 2018. Retrieved 2018-08-16 .
^ a b Inoue K, Mizuo H, Kawaguchi S, Fukuda K, Kusano K, Yoshimura T (August 2014). "Oxidative metabolic pathway of lenvatinib mediated by aldehyde oxidase". Drug Metabolism and Disposition . 42 8 ): 1326–33. doi :10.1124/dmd.114.058073 . PMID 24914245 . S2CID 206497491 .
^ Glen H, Boss D, Evans TR, Roelvink M, et al. (2007). "A phase I dose finding study of E7080 in patients (pts) with advanced malignancies" . Journal of Clinical Oncology, ASCO Annual Meeting Proceedings Part I . 25 the original on 2012-02-24. Retrieved 2009-09-02 .
^ Clinical trial number NCT01321554 ClinicalTrials.gov
^ "Phase III trial shows lenvatinib meets primary endpoint of progression free survival benefit in treatment of radioiodine-refractory differentiated thyroid cancer" (PDF) . Eisai. 3 February 2014.
^ U.S. Food and Drug Administration. Hematology/Oncology (Cancer) Approvals & Safety Notifications. [1 ]
^ "Summary of the European public assessment report (EPAR) for Lenvima" . European Medicines Agency . 17 September 2018. Archived from the original on 20 June 2018. Retrieved 9 January 2016 .
t
e
CI monoclonal antibodies ("-mab")
Tyrosine kinase inhibitors ("-nib")
Receptor tyrosine kinase
RET inhibitors:Entrectinib (ALK, ROS1, NTRK), Futibatinib (FGFR2), Infigratinib , Larotrectinib (NTRK), Pemigatinib (FGFR), Pralsetinib , Repotrectinib (ROS1, TRK, ALK), Selpercatinib (VEGFR, FGFR), Vandetanib (VEGFR, EGFR).
Non-receptor
Other
t
e
Angiopoietin
CNTF
EGF (ErbB)
FGF
FGFR1
FGFR2
Agonists: Ersofermin
FGF (1 2 (bFGF) , 3 4 5 6 7 KGF ), 8 9 10 (KGF2) , 17 18 22
Palifermin
Repifermin
Selpercatinib
Sprifermin
Trafermin
FGFR3
FGFR4
Unsorted
HGF (c-Met)
IGF
LNGF (p75NTR )
PDGF
RET (GFL)
SCF (c-Kit)
TGFβ
Trk
TrkA
Negative allosteric modulators: VM-902A
TrkB
Agonists: 3,7-DHF
3,7,8,2'-THF
4'-DMA-7,8-DHF
7,3'-DHF
7,8-DHF
7,8,2'-THF
7,8,3'-THF
Amitriptyline
BDNF
BNN-20
Deoxygedunin
Deprenyl
Diosmetin
DMAQ-B1
HIOC
LM22A-4
N-Acetylserotonin
NT-3
NT-4
Norwogonin (5,7,8-THF)
R7
R13
TDP6
TrkC
VEGF
Others
Additional growth factors: Adrenomedullin
Colony-stimulating factors (see here instead)
Connective tissue growth factor (CTGF)
Ephrins (A1 , A2 , A3 , A4 , A5 , B1 , B2 , B3 )
Erythropoietin (see here instead)
Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF)
Glia maturation factor (GMF)
Hepatoma-derived growth factor (HDGF)
Interleukins /T-cell growth factors (see here instead)
Leukemia inhibitory factor (LIF)
Macrophage-stimulating protein (MSP; HLP, HGFLP)
Midkine (NEGF2)
Migration-stimulating factor (MSF; PRG4)
Oncomodulin
Pituitary adenylate cyclase-activating peptide (PACAP)
Pleiotrophin
Renalase
Thrombopoietin (see here instead)
Wnt signaling proteins
Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)
R e t r i e v e d f r o m " https://en.wikipedia.org/w/index.php?title=Lenvatinib&oldid=1218180280 " C a t e g o r i e s : ● P r o t e i n k i n a s e i n h i b i t o r s ● O r p h a n d r u g s ● C y c l o p r o p a n e s ● C h l o r o a r e n e s ● U r e a s ● C a r b o x a m i d e s H i d d e n c a t e g o r i e s : ● C S 1 G e r m a n - l a n g u a g e s o u r c e s ( de ) ● A r t i c l e s w i t h s h o r t d e s c r i p t i o n ● S h o r t d e s c r i p t i o n m a t c h e s W i k i d a t a ● D r u g s w i t h n o n - s t a n d a r d l e g a l s t a t u s ● A r t i c l e s w i t h c h a n g e d C A S N o i d e n t i f i e r ● A r t i c l e s w i t h c h a n g e d D r u g B a n k i d e n t i f i e r ● A r t i c l e s w i t h c h a n g e d K E G G i d e n t i f i e r ● A r t i c l e s w i t h c h a n g e d E B I i d e n t i f i e r ● M u l t i p l e c h e m i c a l s i n I n f o b o x d r u g ● C h e m i c a l s u s i n g i n d e x l a b e l s ● D r u g b o x e s w h i c h c o n t a i n c h a n g e s t o v e r i f i e d f i e l d s ● D r u g b o x e s w h i c h c o n t a i n c h a n g e s t o w a t c h e d f i e l d s
● T h i s p a g e w a s l a s t e d i t e d o n 1 0 A p r i l 2 0 2 4 , a t 0 6 : 0 0 ( U T C ) . ● T e x t i s a v a i l a b l e u n d e r t h e C r e a t i v e C o m m o n s A t t r i b u t i o n - S h a r e A l i k e L i c e n s e 4 . 0 ;
a d d i t i o n a l t e r m s m a y a p p l y . B y u s i n g t h i s s i t e , y o u a g r e e t o t h e T e r m s o f U s e a n d P r i v a c y P o l i c y . W i k i p e d i a ® i s a r e g i s t e r e d t r a d e m a r k o f t h e W i k i m e d i a F o u n d a t i o n , I n c . , a n o n - p r o f i t o r g a n i z a t i o n . ● P r i v a c y p o l i c y ● A b o u t W i k i p e d i a ● D i s c l a i m e r s ● C o n t a c t W i k i p e d i a ● C o d e o f C o n d u c t ● D e v e l o p e r s ● S t a t i s t i c s ● C o o k i e s t a t e m e n t ● M o b i l e v i e w
N
Y (what is this?) (verify)
