Identification

Name
Lenvatinib
Accession Number
DB09078
Type
Small Molecule
Groups
Approved, Investigational
Description

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.

Structure
Thumb
Synonyms
  • 4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxamide
External IDs
E 7080 / E-7080 / E7080 / ER-203492-00 / UNII-EE083865G2
Product Ingredients
IngredientUNIICASInChI Key
Lenvatinib Mesylate3J78384F61Not AvailableNot applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LenvimaCapsule10 mgOralEisai Limited2016-03-31Not applicableCanada
LenvimaCapsule24 mgOralEisai Limited2016-03-31Not applicableCanada
LenvimaCapsule4 mg/1OralEisai Inc.2016-05-13Not applicableUs
LenvimaCapsule8 mgOralEisai LimitedNot applicableNot applicableCanada
LenvimaCapsule14 mgOralEisai Limited2016-03-31Not applicableCanada
LenvimaCapsule4 mg/1OralEisai Inc.2018-08-15Not applicableUs
LenvimaCapsule10 mg/1OralEisai Inc.2015-02-13Not applicableUs
LenvimaCapsule18 mgOralEisai LimitedNot applicableNot applicableCanada
LenvimaCapsule20 mgOralEisai Limited2016-03-31Not applicableCanada
LenvimaCapsule4 mg/1OralEisai Inc.2018-08-15Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
LenvimaLenvatinib (10 mg/1) + Lenvatinib (4 mg/1)KitEisai Inc.2015-02-13Not applicableUs
LenvimaLenvatinib (10 mg/1) + Lenvatinib (4 mg/1)KitEisai Inc.2015-02-13Not applicableUs
LenvimaLenvatinib (10 mg/1) + Lenvatinib (4 mg/1)KitEisai Inc.2016-05-13Not applicableUs
LenvimaLenvatinib (10 mg/1) + Lenvatinib (4 mg/1)KitEisai Inc.2015-02-13Not applicableUs
LenvimaLenvatinib (10 mg/1) + Lenvatinib (4 mg/1)KitEisai Inc.2016-05-13Not applicableUs
LenvimaLenvatinib (10 mg/1) + Lenvatinib (4 mg/1)KitEisai Inc.2015-02-13Not applicableUs
Categories
UNII
EE083865G2
CAS number
417716-92-8
Weight
Average: 426.86
Monoisotopic: 426.1094828
Chemical Formula
C21H19ClN4O4
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-[(cyclopropyl-C-hydroxycarbonimidoyl)amino]phenoxy}-7-methoxyquinoline-6-carboximidic acid
SMILES
COC1=C(C=C2C(OC3=CC(Cl)=C(NC(O)=NC4CC4)C=C3)=CC=NC2=C1)C(O)=N

Pharmacology

Indication

Lenvatinib is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer.

Associated Conditions
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
Human
AVascular endothelial growth factor receptor 2
inhibitor
Human
AVascular endothelial growth factor receptor 3
inhibitor
Human
AFibroblast growth factor receptor 1
inhibitor
Human
AFibroblast growth factor receptor 2
inhibitor
Human
AFibroblast growth factor receptor 3
inhibitor
Human
AFibroblast growth factor receptor 4
inhibitor
Human
APlatelet derived growth factor receptor alpha
inhibitor
Human
ARET
inhibitor
Human
AMast/stem cell growth factor receptor Kit
inhibitor
Human
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
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.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Lenvatinib.
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Lenvatinib.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Lenvatinib.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Lenvatinib.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Lenvatinib.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Lenvatinib.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Lenvatinib.
AbemaciclibAbemaciclib may decrease the excretion rate of Lenvatinib which could result in a higher serum level.
AbexinostatThe risk or severity of QTc prolongation can be increased when Lenvatinib is combined with Abexinostat.
AbirateroneThe metabolism of Abiraterone can be increased when combined with Lenvatinib.
Food Interactions
Not Available

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. [PubMed:17943726]
  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. [PubMed:21781317]
  3. Scott LJ: Lenvatinib: first global approval. Drugs. 2015 Apr;75(5):553-60. doi: 10.1007/s40265-015-0383-0. [PubMed:25795101]
  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. [PubMed:25707627]
External Links
KEGG Drug
D09920
PubChem Compound
9823820
PubChem Substance
310265006
ChemSpider
7999567
BindingDB
50331094
ChEBI
85994
ChEMBL
CHEMBL1289601
PharmGKB
PA166153472
HET
LEV
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lenvatinib
ATC Codes
L01XE29 — Lenvatinib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
3wzd / 5zv2
FDA label
Download (388 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentSolid Tumor or Lymphoma1
1Active Not RecruitingTreatmentTumors1
1Active Not RecruitingTreatmentTumors, Solid1
1Active Not RecruitingTreatmentUnresectable Hepatocellular Carcinoma (HCC)1
1CompletedBasic ScienceMalignant Lymphomas / Refractory Solid Tumors1
1CompletedTreatmentAdvanced Solid Tumors / Malignant Lymphomas1
1CompletedTreatmentCancer: Solid Tumors1
1CompletedTreatmentCancers2
1CompletedTreatmentDisease Severity / Impaired Renal Function1
1CompletedTreatmentHealthy Volunteers3
1CompletedTreatmentHealthy Volunteers / P-glycoprotein1
1CompletedTreatmentHepatic Function / Hepatic Impairment1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedTreatmentMetastatic Melanoma1
1Not Yet RecruitingTreatmentCancer, Advanced / Malignant Neoplasm of Breast / Malignant Neoplasms of Bone and Articular Cartilage / Malignant Neoplasms of Digestive Organs / Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System / Malignant Neoplasms of Female Genital Organs / Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites / Malignant Neoplasms of Independent (Primary) Multiple Sites / Malignant Neoplasms of Lip Oral Cavity and Pharynx / Malignant Neoplasms of Male Genital Organs / Malignant Neoplasms of Mesothelial and Soft Tissue / Malignant Neoplasms of Respiratory and Intrathoracic Organs / Malignant Neoplasms of Thyroid and Other Endocrine Glands / Malignant Neoplasms of Urinary Tract1
1Not Yet RecruitingTreatmentTumors, Solid1
1RecruitingTreatmentFallopian Tube Carcinoma / Primary Peritoneal Carcinoma / Recurrent Endometrial Cancer / Recurrent Ovarian Cancer1
1RecruitingTreatmentHepatocellular,Carcinoma2
1RecruitingTreatmentRectal Adenocarcinoma / Rectal Carcinoma1
1TerminatedTreatmentRenal Cell Adenocarcinoma1
1, 2Active Not RecruitingTreatmentMetastatic Renal Cell Carcinoma1
1, 2CompletedTreatmentHepatocellular,Carcinoma1
1, 2CompletedTreatmentStage IV Melanoma1
1, 2RecruitingTreatmentCancer, Advanced / Leiomyosarcomas / Liposarcoma / Soft Tissue Sarcoma Adult1
1, 2RecruitingTreatmentCancer, Breast1
1, 2RecruitingTreatmentDifferentiated Thyroid Cancer (DTC) / Sarcoma, Osteogenic / Solid Malignant Tumors / Tumors1
1, 2RecruitingTreatmentRecurrent and Refractory Solid Tumors1
1, 2RecruitingTreatmentTumors1
1, 2TerminatedTreatmentCancer of the Ovary1
2Active Not RecruitingTreatmentAdenoid Cystic Carcinomas of the Salivary Glands1
2Active Not RecruitingTreatmentBiliary Tract Cancer1
2Active Not RecruitingTreatmentCarcinoma, Adenoid Cystic1
2Active Not RecruitingTreatmentThyroid Cancer, Anaplastic1
2CompletedTreatmentEndometrial Cancers1
2CompletedTreatmentGliomas1
2CompletedTreatmentKIF5B-RET-Positive Adenocarcinoma of the Lung1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2CompletedTreatmentNeuroendocrine Tumors1
2CompletedTreatmentStage IV Melanoma / Unresectable Stage III1
2CompletedTreatmentThyroid Cancers2
2Not Yet RecruitingTreatmentAdvanced Gastric Cancer1
2Not Yet RecruitingTreatmentDifferentiated Thyroid Gland Carcinoma / Thyroid Gland Follicular Carcinoma / Thyroid Gland Papillary Carcinoma1
2Not Yet RecruitingTreatmentRenal Cell Adenocarcinoma1
2RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Gastric Adenocarcinoma / Recurrent Gastric Carcinoma / Stage IV Gastric Cancer AJCC v71
2RecruitingTreatmentAdvanced Non-Small Cell Lung Cancer1
2RecruitingTreatmentAnaplastic Thyroid Cancers1
2RecruitingTreatmentCancer, Breast1
2RecruitingTreatmentCancers / Tumors, Solid1
2RecruitingTreatmentColumnar Cell Variant Thyroid Gland Papillary Carcinoma / Follicular Variant Thyroid Gland Papillary Carcinoma / Poorly Differentiated Thyroid Gland Carcinoma / Recurrent Thyroid Gland Carcinoma / Stage III Differentiated Thyroid Gland Carcinoma / Stage III Differentiated Thyroid Gland Carcinoma AJCC v7 / Stage III Thyroid Gland Follicular Carcinoma / Stage III Thyroid Gland Follicular Carcinoma AJCC v7 / Stage III Thyroid Gland Papillary Carcinoma / Stage III Thyroid Gland Papillary Carcinoma AJCC v7 / Stage IV Thyroid Gland Follicular Carcinoma / Stage IV Thyroid Gland Follicular Carcinoma AJCC v7 / Stage IV Thyroid Gland Papillary Carcinoma / Stage IV Thyroid Gland Papillary Carcinoma AJCC v7 / Stage IVA Differentiated Thyroid Gland Carcinoma / Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7 / Stage IVA Thyroid Gland Follicular Carcinoma / Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7 / Stage IVA Thyroid Gland Papillary Carcinoma / Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7 / Stage IVB Differentiated Thyroid Gland Carcinoma / Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7 / Stage IVB Thyroid Gland Follicular Carcinoma / Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7 / Stage IVB Thyroid Gland Papillary Carcinoma / Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7 / Stage IVC Differentiated Thyroid Gland Carcinoma / Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7 / Stage IVC Thyroid Gland Follicular Carcinoma / Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7 / Stage IVC Thyroid Gland Papillary Carcinoma / Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7 / Tall Cell Variant Thyroid Gland Papillary Carcinoma / Thyroid Gland Oncocytic Follicular Carcinoma1
2RecruitingTreatmentDifferentiated Thyroid Cancer (DTC) / Follicular Thyroid Cancer / Poorly Differentiated Thyroid Gland Carcinoma / Thyroid Cancer, Medullary / Thyroid Cancers / Thyroid Papillary Carcinoma1
2RecruitingTreatmentGastrooesophageal Cancer1
2RecruitingTreatmentHepatocellular,Carcinoma1
2RecruitingTreatmentMalignant Adrenal Gland Pheochromocytoma / Metastatic Adrenal Gland Pheochromocytoma / Paraganglion neoplasm malignant1
2RecruitingTreatmentNon Clear Cell Renal Cell Carcinoma (nccRCC)1
2RecruitingTreatmentRenal Cell Adenocarcinoma1
2RecruitingTreatmentThyroid Cancers2
2WithdrawnTreatmentCancers1
2WithdrawnTreatmentNeoplasms, Endometrial1
3Active Not RecruitingTreatmentHepatocellular Carcinoma (HCC)1
3Active Not RecruitingTreatmentThyroid Cancers1
3RecruitingTreatmentDifferentiated Thyroid Cancer (DTC)1
3RecruitingTreatmentNeoplasms, Endometrial1
3RecruitingTreatmentRenal Cell Adenocarcinoma1
4RecruitingTreatmentNeoplasms, Thyroid1
Not AvailableActive Not RecruitingDiagnosticAdvanced Cancers / Endocrine Tumors1
Not AvailableApproved for MarketingNot AvailableDifferentiated Thyroid Cancer (DTC)1
Not AvailableApproved for MarketingNot AvailableThyroid Cancers1
Not AvailableRecruitingNot AvailableHepatocellular,Carcinoma1
Not AvailableRecruitingNot AvailableNeoplasms, Thyroid1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral10 mg
CapsuleOral10 mg/1
CapsuleOral14 mg
CapsuleOral18 mg
CapsuleOral20 mg
CapsuleOral24 mg
CapsuleOral4 mg/1
CapsuleOral8 mg
Kit
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9006256No2007-07-272027-07-27Us
US7253286No2001-10-192021-10-19Us
US7612208No2006-09-192026-09-19Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP3.30FDA Label
pKa5.05FDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.0177 mg/mLALOGPS
logP3.25ALOGPS
logP2.16ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)3.56ChemAxon
pKa (Strongest Basic)6.1ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area120.05 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity123.67 m3·mol-1ChemAxon
Polarizability42.74 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/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Quinoline-6-carboxamide / Diaryl ether / N-phenylurea / Phenoxy compound / Anisole / Phenol ether / Alkyl aryl ether / Halobenzene / Chlorobenzene / Aryl chloride
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aromatic ether, quinolines, ureas, monocarboxylic acid amide, cyclopropanes, monochlorobenzenes, aromatic amide (CHEBI:85994)

Targets

Kind
Protein
Organism
Human
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. [PubMed:17943726]
Kind
Protein
Organism
Human
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. [PubMed:17943726]
Kind
Protein
Organism
Human
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. [PubMed:17943726]
Kind
Protein
Organism
Human
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. [PubMed:17943726]
Kind
Protein
Organism
Human
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. [PubMed:17943726]
Kind
Protein
Organism
Human
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. [PubMed:17943726]
Kind
Protein
Organism
Human
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. [PubMed:17943726]
8. Platelet derived growth factor receptor alpha
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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. [PubMed:17943726]
9. RET
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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. [PubMed:17943726]
Kind
Protein
Organism
Human
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. [PubMed:17943726]

Enzymes

Kind
Protein
Organism
Human
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
Human
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
Human
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. [PubMed:26721703]
Kind
Protein
Organism
Human
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
Human
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
Human
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
Human
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
Human
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
Human
Pharmacological action
No
Actions
Substrate
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
Kind
Protein
Organism
Human
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
Human
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
Human
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
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
Kind
Protein
Organism
Human
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
Human
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
Human
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

Drug created on June 22, 2015 07:20 / Updated on October 18, 2018 16:25