You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameRegorafenib
Accession NumberDB08896
TypeSmall Molecule
GroupsApproved
Description

Regorafenib is an orally-administered inhibitor of multiple kinases. It is used for the treatment of metastatic colorectal cancer and advanced gastrointestinal stromal tumours. FDA approved on September 27, 2012.

Structure
Thumb
Synonyms
BAY 73-4506
Regorafenibum
External Identifiers
  • BAY 73-4506
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Stivargatablet40 mgoralBayer Inc2013-04-02Not applicableCanada
Stivargatablet, film coated40 mg/1oralBayer Health Care Pharmaceuticals Inc.2012-09-27Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Regorafenib monohydrate
ThumbNot applicableDBSALT001750
Categories
UNII24T2A1DOYB
CAS number755037-03-7
WeightAverage: 482.815
Monoisotopic: 482.076880893
Chemical FormulaC21H15ClF4N4O3
InChI KeyInChIKey=FNHKPVJBJVTLMP-UHFFFAOYSA-N
InChI
InChI=1S/C21H15ClF4N4O3/c1-27-19(31)18-10-13(6-7-28-18)33-12-3-5-17(16(23)9-12)30-20(32)29-11-2-4-15(22)14(8-11)21(24,25)26/h2-10H,1H3,(H,27,31)(H2,29,30,32)
IUPAC Name
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide
SMILES
CNC(=O)C1=CC(OC2=CC(F)=C(NC(=O)NC3=CC=C(Cl)C(=C3)C(F)(F)F)C=C2)=CC=N1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
KingdomOrganic compounds
Super ClassOrganooxygen compounds
ClassEthers
Sub ClassDiarylethers
Direct ParentDiarylethers
Alternative Parents
Substituents
  • Diaryl ether
  • N-phenylurea
  • Pyridine carboxylic acid or derivatives
  • Pyridinecarboxamide
  • Halobenzene
  • Fluorobenzene
  • Chlorobenzene
  • Benzenoid
  • Pyridine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl fluoride
  • Aryl chloride
  • Heteroaromatic compound
  • Urea
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organofluoride
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationRegorafenib is indicated for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. Regorafenib is also indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.
PharmacodynamicsNot Available
Mechanism of actionRegorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment. In in vitro biochemical or cellular assays, regorafenib or its major human active metabolites M-2 and M-5 inhibited the activity of RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, TrkA, Eph2A, RAF-1, BRAF, BRAFV600E , SAPK2, PTK5, and Abl at concentrations of regorafenib that have been achieved clinically. In in vivo models, regorafenib demonstrated anti-angiogenic activity in a rat tumor model, and inhibition of tumor growth as well as anti-metastatic activity in several mouse xenograft models including some for human colorectal carcinoma.
Related Articles
AbsorptionCmax = 2.5 μg/mL; Tmax = 4 hours; AUC = 70.4 μg*h/mL; Cmax, steady-state = 3.9 μg/mL; AUC, steady-state = 58.3 μg*h/mL; The mean relative bioavailability of tablets compared to an oral solution is 69% to 83%.
Volume of distribution

Regorafenib undergoes enterohepatic circulation with multiple plasma concentration peaks observed across the 24-hour dosing interval.

Protein bindingRegorafenib is highly bound (99.5%) to human plasma proteins.
Metabolism

Regorafenib is metabolized by CYP3A4 and UGT1A9. The main circulating metabolites of regorafenib measured at steady-state in human plasma are M-2 (N-oxide) and M-5 (N-oxide and N-desmethyl), both of them having similar in vitro pharmacological activity and steady-state concentrations as regorafenib. M-2 and M-5 are highly protein bound (99.8% and 99.95%, respectively).

Route of eliminationApproximately 71% of a radiolabeled dose was excreted in feces (47% as parent compound, 24% as metabolites) and 19% of the dose was excreted in urine (17% as glucuronides) within 12 days after administration of a radiolabeled oral solution at a dose of 120 mg.
Half lifeRegorafenib, 160 mg oral dose = 28 hours (14 - 58 hours); M2 metabolite, 160 mg oral dose = 25 hours (14-32 hours); M5 metabolite, 160 mg oral dose = 51 hours (32-72 hours);
ClearanceNot Available
ToxicityThe most common adverse reactions (≥20%) are asthenia/fatigue, HFSR, diarrhea, decreased appetite/food intake, hypertension, mucositis, dysphonia, and infection, pain (not otherwise specified), decreased weight, gastrointestinal and abdominal pain, rash, fever, and nausea
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9649
Blood Brain Barrier+0.851
Caco-2 permeable-0.5138
P-glycoprotein substrateNon-substrate0.5086
P-glycoprotein inhibitor INon-inhibitor0.7141
P-glycoprotein inhibitor IINon-inhibitor0.9359
Renal organic cation transporterNon-inhibitor0.8938
CYP450 2C9 substrateNon-substrate0.6569
CYP450 2D6 substrateNon-substrate0.8212
CYP450 3A4 substrateNon-substrate0.5341
CYP450 1A2 substrateInhibitor0.6168
CYP450 2C9 inhibitorNon-inhibitor0.6171
CYP450 2D6 inhibitorNon-inhibitor0.9145
CYP450 2C19 inhibitorInhibitor0.637
CYP450 3A4 inhibitorNon-inhibitor0.7339
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6629
Ames testNon AMES toxic0.8143
CarcinogenicityNon-carcinogens0.8684
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7885 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9488
hERG inhibition (predictor II)Non-inhibitor0.6415
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tabletoral40 mg
Tablet, film coatedoral40 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2315715 No2010-06-222018-12-22Canada
CA2526636 No2012-10-022024-05-19Canada
CA2549558 No2010-08-312020-01-12Canada
US7351834 No2000-01-122020-01-12Us
US8637553 No2011-02-162031-02-16Us
US8680124 No2010-06-022030-06-02Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityInsoluble FDA label
Predicted Properties
PropertyValueSource
Water Solubility0.00102 mg/mLALOGPS
logP4.53ALOGPS
logP4.49ChemAxon
logS-5.7ALOGPS
pKa (Strongest Acidic)10.52ChemAxon
pKa (Strongest Basic)2.02ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area92.35 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity114.73 m3·mol-1ChemAxon
Polarizability41.23 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesL01XE21
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (457 KB)
MSDSDownload (479 KB)
Interactions
Drug Interactions
Drug
AcebutololRegorafenib may increase the bradycardic activities of Acebutolol.
AprepitantThe serum concentration of Regorafenib can be increased when it is combined with Aprepitant.
AtazanavirThe serum concentration of Regorafenib can be increased when it is combined with Atazanavir.
AtenololRegorafenib may increase the bradycardic activities of Atenolol.
BepridilRegorafenib may increase the bradycardic activities of Bepridil.
BetaxololRegorafenib may increase the bradycardic activities of Betaxolol.
BexaroteneThe serum concentration of Regorafenib can be decreased when it is combined with Bexarotene.
BisoprololRegorafenib may increase the bradycardic activities of Bisoprolol.
BoceprevirThe serum concentration of Regorafenib can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Regorafenib can be decreased when it is combined with Bosentan.
CarbamazepineThe serum concentration of Regorafenib can be decreased when it is combined with Carbamazepine.
CarteololRegorafenib may increase the bradycardic activities of Carteolol.
CarvedilolRegorafenib may increase the bradycardic activities of Carvedilol.
CeritinibThe serum concentration of Regorafenib can be increased when it is combined with Ceritinib.
ClarithromycinThe serum concentration of Regorafenib can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Regorafenib can be increased when it is combined with Cobicistat.
ConivaptanThe serum concentration of Regorafenib can be increased when it is combined with Conivaptan.
DabrafenibThe serum concentration of Regorafenib can be decreased when it is combined with Dabrafenib.
DarunavirThe serum concentration of Regorafenib can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Regorafenib can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Regorafenib can be decreased when it is combined with Deferasirox.
DigoxinRegorafenib may increase the bradycardic activities of Digoxin.
DiltiazemRegorafenib may increase the bradycardic activities of Diltiazem.
EnzalutamideThe serum concentration of Regorafenib can be decreased when it is combined with Enzalutamide.
EsmololRegorafenib may increase the bradycardic activities of Esmolol.
FluconazoleThe metabolism of Regorafenib can be decreased when combined with Fluconazole.
FosaprepitantThe serum concentration of Regorafenib can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Regorafenib can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Regorafenib can be increased when it is combined with Fusidic Acid.
IdelalisibThe serum concentration of Regorafenib can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Regorafenib can be increased when it is combined with Indinavir.
IrinotecanThe serum concentration of the active metabolites of Irinotecan can be increased when Irinotecan is used in combination with Regorafenib.
ItraconazoleThe serum concentration of Regorafenib can be increased when it is combined with Itraconazole.
IvabradineRegorafenib may increase the bradycardic activities of Ivabradine.
IvacaftorThe serum concentration of Regorafenib can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Regorafenib can be increased when it is combined with Ketoconazole.
LabetalolRegorafenib may increase the bradycardic activities of Labetalol.
LevobunololRegorafenib may increase the bradycardic activities of Levobunolol.
LuliconazoleThe serum concentration of Regorafenib can be increased when it is combined with Luliconazole.
MetipranololRegorafenib may increase the bradycardic activities of Metipranolol.
MetoprololRegorafenib may increase the bradycardic activities of Metoprolol.
MifepristoneThe serum concentration of Regorafenib can be increased when it is combined with Mifepristone.
MitotaneThe serum concentration of Regorafenib can be decreased when it is combined with Mitotane.
NadololRegorafenib may increase the bradycardic activities of Nadolol.
NebivololRegorafenib may increase the bradycardic activities of Nebivolol.
NefazodoneThe serum concentration of Regorafenib can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Regorafenib can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Regorafenib can be increased when it is combined with Netupitant.
PalbociclibThe serum concentration of Regorafenib can be increased when it is combined with Palbociclib.
PamidronateThe risk or severity of adverse effects can be increased when Regorafenib is combined with Pamidronate.
PenbutololRegorafenib may increase the bradycardic activities of Penbutolol.
PhenobarbitalThe serum concentration of Regorafenib can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Regorafenib can be decreased when it is combined with Phenytoin.
PindololRegorafenib may increase the bradycardic activities of Pindolol.
PosaconazoleThe serum concentration of Regorafenib can be increased when it is combined with Posaconazole.
PrimidoneThe serum concentration of Regorafenib can be decreased when it is combined with Primidone.
PropranololRegorafenib may increase the bradycardic activities of Propranolol.
RifabutinThe serum concentration of Regorafenib can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Regorafenib can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Regorafenib can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Regorafenib can be increased when it is combined with Ritonavir.
SaquinavirThe serum concentration of Regorafenib can be increased when it is combined with Saquinavir.
SiltuximabThe serum concentration of Regorafenib can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Regorafenib can be increased when it is combined with Simeprevir.
SotalolRegorafenib may increase the bradycardic activities of Sotalol.
St. John's WortThe serum concentration of Regorafenib can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Regorafenib can be increased when it is combined with Stiripentol.
TelaprevirThe serum concentration of Regorafenib can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Regorafenib can be increased when it is combined with Telithromycin.
TimololRegorafenib may increase the bradycardic activities of Timolol.
TocilizumabThe serum concentration of Regorafenib can be decreased when it is combined with Tocilizumab.
VerapamilRegorafenib may increase the bradycardic activities of Verapamil.
VoriconazoleThe serum concentration of Regorafenib can be increased when it is combined with Voriconazole.
WarfarinThe risk or severity of adverse effects can be increased when Warfarin is combined with Regorafenib.
Food Interactions
  • When taken with a high-fat meal, AUC increased by 48% and decreased mean AUC of M2 and M5 metabolites by 20% and 51% respectively.

Targets

Kind
Protein
Organism
Human
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 derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during in...
Gene Name:
RET
Uniprot ID:
P07949
Molecular Weight:
124317.465 Da
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 survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation ...
Gene Name:
FLT1
Uniprot ID:
P17948
Molecular Weight:
150767.185 Da
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 embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domai...
Gene Name:
KDR
Uniprot ID:
P35968
Molecular Weight:
151525.555 Da
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 cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced pr...
Gene Name:
FLT4
Uniprot ID:
P35916
Molecular Weight:
152755.94 Da
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 maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1...
Gene Name:
KIT
Uniprot ID:
P10721
Molecular Weight:
109863.655 Da
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 PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for...
Gene Name:
PDGFRA
Uniprot ID:
P16234
Molecular Weight:
122668.46 Da
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Vascular endothelial growth factor binding
Specific Function:
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of peri...
Gene Name:
PDGFRB
Uniprot ID:
P09619
Molecular Weight:
123966.895 Da
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 and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (...
Gene Name:
FGFR1
Uniprot ID:
P11362
Molecular Weight:
91866.935 Da
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 apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an...
Gene Name:
FGFR2
Uniprot ID:
P21802
Molecular Weight:
92024.29 Da
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 ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of proinflammatory plasma proteins and leukocytes from ...
Gene Name:
TEK
Uniprot ID:
Q02763
Molecular Weight:
125829.005 Da
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Transmembrane receptor protein tyrosine kinase activity
Specific Function:
Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription fa...
Gene Name:
DDR2
Uniprot ID:
Q16832
Molecular Weight:
96735.44 Da
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Transmembrane receptor protein tyrosine kinase activity
Specific Function:
Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand, it can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 ...
Gene Name:
NTRK1
Uniprot ID:
P04629
Molecular Weight:
87496.465 Da
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Transmembrane receptor protein tyrosine kinase activity
Specific Function:
Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the lig...
Gene Name:
EPHA2
Uniprot ID:
P29317
Molecular Weight:
108265.585 Da
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Protein serine/threonine kinase activity
Specific Function:
Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that com...
Gene Name:
RAF1
Uniprot ID:
P04049
Molecular Weight:
73051.025 Da
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Protein serine/threonine kinase activity
Specific Function:
Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron. Phosphorylates MAP2K1, and thereby contributes to the MAP kinase signal transduction pathway.
Gene Name:
BRAF
Uniprot ID:
P15056
Molecular Weight:
84436.135 Da
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Protein serine/threonine kinase activity
Specific Function:
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad r...
Gene Name:
MAPK11
Uniprot ID:
Q15759
Molecular Weight:
41356.875 Da
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Receptor binding
Specific Function:
Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on 'Tyr-336', which in turn prevents its ubiquitination and degradation, possibly by reducing its binding to NEDD4. May function as a tumor suppressor.
Gene Name:
FRK
Uniprot ID:
P42685
Molecular Weight:
58253.61 Da
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Syntaxin binding
Specific Function:
Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 ...
Gene Name:
ABL1
Uniprot ID:
P00519
Molecular Weight:
122871.435 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Retinoic acid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Gene Name:
UGT1A9
Uniprot ID:
O60656
Molecular Weight:
59940.495 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 unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naph...
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular Weight:
59590.91 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
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
Molecular Weight:
141477.255 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
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 from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
Comments
comments powered by Disqus
Drug created on June 03, 2013 16:30 / Updated on June 26, 2016 01:53