Lenvatinib

Identification

Summary

Lenvatinib is a receptor tyrosine kinase inhibitor used for the treatment of metastatic thyroid cancer, advanced renal cell carcinoma in combination with everolimus, and unresectable hepatocellular carcinoma.

Brand Names
Lenvima 10
Generic Name
Lenvatinib
DrugBank Accession Number
DB09078
Background

Lenvatinib 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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 426.86
Monoisotopic: 426.1094828
Chemical Formula
C21H19ClN4O4
Synonyms
  • 4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxamide
  • Lenvatinib
External IDs
  • E 7080
  • E-7080
  • E7080
  • ER-203492-00

Pharmacology

Indication

Lenvatinib is indicated for the treatment of the following cancerous conditions:5

Differentiated Thyroid Cancer (DTC)

  • Treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer

Renal Cell Carcinoma (RCC)

  • First-line treatment, in combination with pembrolizumab, in adult patients with advanced renal cell carcinoma (RCC)
  • Treatment of advanced renal cell carcinoma, in combination with everolimus, in adult patients who have previously tried ≥1 anti-angiogenic therapy

Hepatocellular Carcinoma (HCC)

  • First-line treatment of patients with unresectable hepatocellular carcinoma

Endometrial Carcinoma

  • Treatment of advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), in combination with pembrolizumab, in patients who have experienced disease progression following prior systemic therapy and are not candidates for curative surgery or radiation
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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatAdvanced renal cell carcinoma (arcc)Regimen in combination with: Everolimus (DB01590)••••••••••••••••••••••••• ••••••••••••••• ••••••••••••••
Used in combination to treatAdvanced renal cell carcinoma (arcc)Regimen in combination with: Pembrolizumab (DB09037)••••••••••••••••••••••••
Used in combination to treatEndometrial carcinomaRegimen in combination with: Pembrolizumab (DB09037)••••••••••••••• • ••••••••• ••• •••••••• ••••••• •• •••••••••• ••••••• ••••••••••• ••••• •••••••• •••••••••• •••••••• •••••• •••••••••••••••••
Used in combination to treatUnresectable hepatocellular carcinoma (hcc)•••••••••••••••••••
Treatment ofProgressive, locally advanced radioactive iodine-refractory differentiated thyroid cancer (dtc)•••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Based on x-ray crystallography and kinetic interaction studies, lenvatinib binds to the adenosine 5'-triphosphate binding site of VEGFR2 and to a neighbouring region via a cyclopropane ring and thereby inhibits tyrosine kinase activity and associated signalling pathways.

Mechanism of action

Lenvatinib 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.

TargetActionsOrganism
AVascular endothelial growth factor receptor 1
inhibitor
Humans
AVascular endothelial growth factor receptor 2
inhibitor
Humans
AVascular endothelial growth factor receptor 3
inhibitor
Humans
AFibroblast growth factor receptor 1
inhibitor
Humans
AFibroblast growth factor receptor 2
inhibitor
Humans
AFibroblast growth factor receptor 3
inhibitor
Humans
AFibroblast growth factor receptor 4
inhibitor
Humans
APlatelet-derived growth factor receptor alpha
inhibitor
Humans
AProto-oncogene tyrosine-protein kinase receptor Ret
inhibitor
Humans
AMast/stem cell growth factor receptor Kit
inhibitor
Humans
Absorption

Time to peak plasma concentration occurred from 1 to 4 hours post­dose. Administration with food did not affect the extent of absorption, but decreased the rate of absorption and delayed the median Tmax from 2 hours to 4 hours.

Volume of distribution

Not Available

Protein binding

In vitro binding of lenvatinib to human plasma proteins ranged from 98% to 99%.

Metabolism

Lenvatinib is metabolized by CYP3A and aldehyde oxidase.

Route of elimination

Following administration of a radiolabeled dose, approximately 64% and 25% of the radiolabel were eliminated in the feces and urine, respectively.

Half-life

The terminal elimination half­life of lenvatinib is approximately 28 hours.

Clearance

Not Available

Adverse Effects
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Toxicity

The most common adverse events that occurred in lenvatinib recipients were hypertension (67.8 vs. 9.2 % in the placebo group), diarrhea (59.4 vs. 8.4 %), fatigue or asthenia (59.0 vs. 27.5 %), decreased appetite (50.2 vs. 11.5 %), decreased bodyweight (46.4 vs. 9.2 %), nausea (41.0 vs. 13.7 %), stomatitis (35.6 vs. 3.8 %), palmar-plantar erythrodysethesia syndrome (31.8 vs. 8.0 %) and proteinuria (31.0 vs. 1.5 %). Adverse events that occurred in clinical trials and for which there is a warning/precaution in US manufacturer’s pre- scribing information were hypertension, cardiac dysfunction (decreased left or right ventricular function, cardiac failure or pulmonary edema), arterial thromboembolic events, hepatotoxicity, proteinuria, renal failure and impairment, gastrointestinal perforation and fistula formation, QT interval prolongation, hypocalcaemia, reversible posterior leucoencephalopathy syndrome, haemorrhagic events, and impairment of thyroid stimulating hormone (TSH) suppression. Based on the mechanism of action of lenvatinib and results from animal reproduction studies, which showed embryotoxicity, foetotoxicity and teratogenicity at lenvatinib doses below the recommended dose in humans, females of reproductive potential should be advised to use effective contraception during treatment and for at least 2 weeks following completion of therapy.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbemaciclibAbemaciclib may decrease the excretion rate of Lenvatinib which could result in a higher serum level.
AbrocitinibThe serum concentration of Lenvatinib can be increased when it is combined with Abrocitinib.
AcamprosateThe excretion of Acamprosate can be decreased when combined with Lenvatinib.
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Lenvatinib.
AcrivastineThe risk or severity of QTc prolongation can be increased when Acrivastine is combined with Lenvatinib.
Food Interactions
  • Avoid hypertensive herbs (e.g. bayberry, blue cohosh, cayenne, ephedra, and licorice). Lenvatinib may cause hypertension as an adverse effect; therefore, there may be additive blood pressure elevation when using hypertensive herbs.
  • Take at the same time every day.
  • Take with or without food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Lenvatinib mesylate3J78384F61857890-39-2HWLFIUUAYLEFCT-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
KisplyxCapsule10 mgOralEisai Limited2020-12-16Not applicableEU flag
KisplyxCapsule4 mgOralEisai Limited2020-12-16Not applicableEU flag
KisplyxCapsule10 mgOralEisai Limited2020-12-16Not applicableEU flag
KisplyxCapsule10 mgOralEisai Limited2020-12-16Not applicableEU flag
KisplyxCapsule4 mgOralEisai Limited2020-12-16Not applicableEU flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
LenvimaLenvatinib (10 mg/1) + Lenvatinib (4 mg/1)Capsule; KitOralEisai Inc.2015-02-13Not applicableUS flag
LenvimaLenvatinib (10 mg/1) + Lenvatinib (4 mg/1)Capsule; KitOralEisai Inc.2015-02-13Not applicableUS flag
LenvimaLenvatinib (10 mg/1) + Lenvatinib (4 mg/1)Capsule; KitOralEisai Inc.2016-05-13Not applicableUS flag
LenvimaLenvatinib (10 mg/1) + Lenvatinib (4 mg/1)Capsule; KitOralEisai Inc.2015-02-13Not applicableUS flag
LenvimaLenvatinib (10 mg/1) + Lenvatinib (4 mg/1)Capsule; KitOralEisai Inc.2016-05-13Not applicableUS flag

Categories

ATC Codes
L01EX08 — Lenvatinib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as quinoline carboxamides. These are quinolines in which the quinoline ring system is substituted by one or more carboxamide groups.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Quinoline carboxamides
Direct Parent
Quinoline carboxamides
Alternative Parents
Diarylethers / N-phenylureas / Phenoxy compounds / Anisoles / Alkyl aryl ethers / Chlorobenzenes / Pyridines and derivatives / Aryl chlorides / Heteroaromatic compounds / Ureas
show 8 more
Substituents
Alkyl aryl ether / Anisole / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carbonic acid derivative / Carbonyl group / Carboxamide group
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aromatic ether, quinolines, ureas, monocarboxylic acid amide, cyclopropanes, monochlorobenzenes, aromatic amide (CHEBI:85994)
Affected organisms
Not Available

Chemical Identifiers

UNII
EE083865G2
CAS number
417716-92-8
InChI Key
WOSKHXYHFSIKNG-UHFFFAOYSA-N
InChI
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)
IUPAC Name
4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxamide
SMILES
COC1=C(C=C2C(OC3=CC=C(NC(=O)NC4CC4)C(Cl)=C3)=CC=NC2=C1)C(N)=O

References

General References
  1. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M: 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 Feb 1;122(3):664-71. [Article]
  2. Glen H, Mason S, Patel H, Macleod K, Brunton VG: E7080, a multi-targeted tyrosine kinase inhibitor suppresses tumor cell migration and invasion. BMC Cancer. 2011 Jul 22;11:309. doi: 10.1186/1471-2407-11-309. [Article]
  3. Scott LJ: Lenvatinib: first global approval. Drugs. 2015 Apr;75(5):553-60. doi: 10.1007/s40265-015-0383-0. [Article]
  4. Killock D: Neuroendocrine cancer: SELECT-lenvatinib in thyroid cancer. Nat Rev Clin Oncol. 2015 Apr;12(4):189. doi: 10.1038/nrclinonc.2015.30. Epub 2015 Feb 24. [Article]
  5. FDA Approved Drug Products: Lenvima (lenvatinib) capsules for oral use [Link]
KEGG Drug
D09919
PubChem Compound
9823820
PubChem Substance
310265006
ChemSpider
7999567
BindingDB
50331094
RxNav
1603296
ChEBI
85994
ChEMBL
CHEMBL1289601
ZINC
ZINC000003816292
PharmGKB
PA166153472
PDBe Ligand
LEV
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lenvatinib
PDB Entries
3wzd / 5zv2
FDA label
Download (388 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentThyroid Neoplasm1
4CompletedTreatmentHepatocellular Carcinoma1
4Enrolling by InvitationTreatmentHepatocellular Carcinoma / Portal Vein Tumor Thrombosis1
4Not Yet RecruitingTreatmentBreast Carcinoma / Endometrium Carcinoma / Ovarian Carcinoma / Renal Cell Carcinoma (RCC) / Thyroid Carcinoma1
4RecruitingTreatmentAdvanced Thyroid Cancer Patients Who Received Target Therapy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral
CapsuleOral10 mg / dose
CapsuleOral10 mg/1
CapsuleOral12 mg / dose
CapsuleOral14 mg / dose
CapsuleOral18 mg / dose
CapsuleOral20 mg / dose
CapsuleOral24 mg / dose
CapsuleOral4 mg / dose
CapsuleOral4 mg/1
CapsuleOral8 mg / dose
Capsule; kitOral
CapsuleOral4.0 mg
CapsuleOral10.0 mg
CapsuleOral4.000 mg
CapsuleOral10 mg
CapsuleOral4 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9006256No2015-04-142027-07-27US flag
US7253286No2007-08-072021-10-19US flag
US7612208No2009-11-032026-09-19US flag
US10259791No2019-04-162035-08-26US flag
US10407393No2019-09-102035-08-26US flag
US11186547No2021-11-302035-08-26US flag
US11090386No2021-08-172036-02-23US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP3.30FDA Label
pKa5.05FDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.00622 mg/mLALOGPS
logP3.03ALOGPS
logP2.52Chemaxon
logS-4.8ALOGPS
pKa (Strongest Acidic)12.37Chemaxon
pKa (Strongest Basic)5.4Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area115.57 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity112.21 m3·mol-1Chemaxon
Polarizability42.29 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-01t9-0000900000-661dd49d62c1a164dfcd
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0kor-9007400000-1e813ee566a7c629488f
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a6r-8009000000-5c2bf3451040dfc11a4b
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-8109100000-c26c9843a6fd52924d6f
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4l-9005200000-f1eef0474b5e1fca3d7c
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-000x-9400000000-fb722f879dd803d64884
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-193.1507
predicted
DeepCCS 1.0 (2019)
[M+H]+195.50871
predicted
DeepCCS 1.0 (2019)
[M+Na]+201.71086
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vegf-b-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
Molecular Weight
150767.185 Da
References
  1. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M: 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 Feb 1;122(3):664-71. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
References
  1. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M: 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 Feb 1;122(3):664-71. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardi...
Gene Name
FLT4
Uniprot ID
P35916
Uniprot Name
Vascular endothelial growth factor receptor 3
Molecular Weight
152755.94 Da
References
  1. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M: 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 Feb 1;122(3):664-71. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation ...
Gene Name
FGFR1
Uniprot ID
P11362
Uniprot Name
Fibroblast growth factor receptor 1
Molecular Weight
91866.935 Da
References
  1. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M: 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 Feb 1;122(3):664-71. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosi...
Gene Name
FGFR2
Uniprot ID
P21802
Uniprot Name
Fibroblast growth factor receptor 2
Molecular Weight
92024.29 Da
References
  1. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M: 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 Feb 1;122(3):664-71. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an...
Gene Name
FGFR3
Uniprot ID
P22607
Uniprot Name
Fibroblast growth factor receptor 3
Molecular Weight
87708.905 Da
References
  1. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M: 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 Feb 1;122(3):664-71. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation o...
Gene Name
FGFR4
Uniprot ID
P22455
Uniprot Name
Fibroblast growth factor receptor 4
Molecular Weight
87953.535 Da
References
  1. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M: 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 Feb 1;122(3):664-71. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chem...
Gene Name
PDGFRA
Uniprot ID
P16234
Uniprot Name
Platelet-derived growth factor receptor alpha
Molecular Weight
122668.46 Da
References
  1. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M: 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 Feb 1;122(3):664-71. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell de...
Gene Name
RET
Uniprot ID
P07949
Uniprot Name
Proto-oncogene tyrosine-protein kinase receptor Ret
Molecular Weight
124317.465 Da
References
  1. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M: 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 Feb 1;122(3):664-71. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
Gene Name
KIT
Uniprot ID
P10721
Uniprot Name
Mast/stem cell growth factor receptor Kit
Molecular Weight
109863.655 Da
References
  1. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M: 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 Feb 1;122(3):664-71. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Xanthine dehydrogenase activity
Specific Function
Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal...
Gene Name
AOX1
Uniprot ID
Q06278
Uniprot Name
Aldehyde oxidase
Molecular Weight
147916.735 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Hussaarts KGAM, Veerman GDM, Jansman FGA, van Gelder T, Mathijssen RHJ, van Leeuwen RWF: Clinically relevant drug interactions with multikinase inhibitors: a review. Ther Adv Med Oncol. 2019 Jan 4;11:1758835918818347. doi: 10.1177/1758835918818347. eCollection 2019. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Hussaarts KGAM, Veerman GDM, Jansman FGA, van Gelder T, Mathijssen RHJ, van Leeuwen RWF: Clinically relevant drug interactions with multikinase inhibitors: a review. Ther Adv Med Oncol. 2019 Jan 4;11:1758835918818347. doi: 10.1177/1758835918818347. eCollection 2019. [Article]

Drug created at June 22, 2015 13:20 / Updated at March 18, 2024 16:48