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Identification
NameDabrafenib
Accession NumberDB08912
TypeSmall Molecule
GroupsApproved
Description

Dabrafenib mesylate is a reversible ATP-competitive kinase inhibitor and targets the MAPK pathway. FDA approved on May 29, 2013.

Structure
Thumb
Synonyms
Dabrafenib
GSK2118436a
External Identifiers
  • GSK2118436
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tafinlarcapsule50 mg/1oralGlaxo Smith Kline Llc2013-06-10Not applicableUs
Tafinlarcapsule50 mg/1oralNovartis Pharmaceuticals Corporation2016-04-12Not applicableUs
Tafinlarcapsule75 mg/1oralNovartis Pharmaceuticals Corporation2016-04-01Not applicableUs
Tafinlarcapsule75 mgoralNovartis Pharmaceuticals Canada Inc2013-08-28Not applicableCanada
Tafinlarcapsule50 mgoralNovartis Pharmaceuticals Canada Inc2013-08-28Not applicableCanada
Tafinlarcapsule75 mg/1oralGlaxo Smith Kline Llc2013-06-10Not 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
Dabrafenib Mesylate
Thumb
  • InChI Key: YKGMKSIHIVVYKY-UHFFFAOYSA-N
  • Monoisotopic Mass: 615.089165588
  • Average Mass: 615.668
DBSALT000036
Categories
UNIIQGP4HA4G1B
CAS numberNot Available
WeightAverage: 519.562
Monoisotopic: 519.101050904
Chemical FormulaC23H20F3N5O2S2
InChI KeyInChIKey=BFSMGDJOXZAERB-UHFFFAOYSA-N
InChI
InChI=1S/C23H20F3N5O2S2/c1-23(2,3)21-30-18(19(34-21)16-10-11-28-22(27)29-16)12-6-4-9-15(17(12)26)31-35(32,33)20-13(24)7-5-8-14(20)25/h4-11,31H,1-3H3,(H2,27,28,29)
IUPAC Name
N-{3-[5-(2-aminopyrimidin-4-yl)-2-tert-butyl-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzene-1-sulfonamide
SMILES
CC(C)(C)C1=NC(=C(S1)C1=NC(N)=NC=C1)C1=C(F)C(NS(=O)(=O)C2=C(F)C=CC=C2F)=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylthiazoles. These are compounds containing a phenylthiazole moiety, which consists of an thiazole ring attached to a phenyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzoles
Sub ClassThiazoles
Direct ParentPhenylthiazoles
Alternative Parents
Substituents
  • Phenylthiazole
  • Sulfanilide
  • Benzenesulfonamide
  • 2,4,5-trisubstituted 1,3-thiazole
  • Halobenzene
  • Fluorobenzene
  • Benzenoid
  • Pyrimidine
  • Primary aromatic amine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl fluoride
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Azacycle
  • Hydrocarbon derivative
  • Primary amine
  • Organosulfur compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationDabrafenib is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.
PharmacodynamicsDabrafenib caused an inhibition of phosphorylated ERK. This indicates a decrease in cell proliferation. Furthermore, within 24 hours of administration, downstream mediators of the MAPK pathway were inhibited.
Mechanism of actionDabrafenib is an inhibitor of some mutated forms of BRAF kinases with in vitro IC50 values of 0.65, 0.5, and 1.84 nM for BRAF V600E, BRAF V600K, and BRAF V600D enzymes, respectively. Dabrafenib also inhibits wild-type BRAF and CRAF kinases with IC50 values of 3.2 and 5.0 nM, respectively, and other kinases such as SIK1, NEK11, and LIMK1 at higher concentrations. Some mutations in the BRAF gene, including those that result in BRAF V600E, can result in constitutively activated BRAF kinases that may stimulate tumor cell growth.
Related Articles
AbsorptionAfter oral administration, median time to achieve peak plasma concentration (Tmax) is 2 hours. Mean absolute bioavailability of oral dabrafenib is 95%.
Volume of distribution

Apparent volume of distribution (Vd/F) = 70.3 L.
Distribution to the brain is restricted because dabrafenib is a substrate and undergoes efflux by P-glycoprotein and breast cancer resistance protein.

Protein binding99.7% bound to human plasma protein.
Metabolism

Dabrafenib is hepatically metabolized. The biotransformation process is primarily mediated by CYP2C8 and CYP3A4 to form hydroxy-debrafenib. This metabolite is further oxidized via CYP3A4 to form carboxy-dabrafenib and subsequently excreted in bile and urine. Carboxy-dabrafenib can also undergo decarboxylation to form desmethyl-dabrafenib, which may be reabsorbed from the gut. Desmethyl-dabrafenib is further metabolized by CYP3A4 to oxidative metabolites.

Route of elimination71% of the dose is excreted in feces. 23% of the dose is excreted in the urine as metabolites only.
Half lifeDabrafenib = 8 hours; Hydroxy-dabrafenib = 10 hours; Carboxy-dabrafenib = 21-22 hours; Desmethyl-dabrafenib = 21- 22 hours.
Clearance

The apparent clearance of dabrafenib is 17.0 L/h after single dosing and 34.4 L/h after 2 weeks of twice daily dosing.

ToxicityMost common adverse reactions (≥20%) for dabrafenib are hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, and palmar-plantar erythrodysesthesia syndrome.
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+0.9944
Blood Brain Barrier+0.7232
Caco-2 permeable+0.5069
P-glycoprotein substrateNon-substrate0.7965
P-glycoprotein inhibitor INon-inhibitor0.6468
P-glycoprotein inhibitor IINon-inhibitor0.7039
Renal organic cation transporterNon-inhibitor0.8694
CYP450 2C9 substrateNon-substrate0.8233
CYP450 2D6 substrateNon-substrate0.7346
CYP450 3A4 substrateNon-substrate0.5834
CYP450 1A2 substrateInhibitor0.5219
CYP450 2C9 inhibitorInhibitor0.5
CYP450 2D6 inhibitorNon-inhibitor0.8459
CYP450 2C19 inhibitorNon-inhibitor0.5
CYP450 3A4 inhibitorInhibitor0.7531
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8612
Ames testNon AMES toxic0.7078
CarcinogenicityNon-carcinogens0.8093
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4329 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9848
hERG inhibition (predictor II)Non-inhibitor0.7704
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsuleoral50 mg/1
Capsuleoral50 mg
Capsuleoral75 mg
Capsuleoral75 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7994185 No2010-01-202030-01-20Us
US8415345 No2010-01-202030-01-20Us
US8703781 No2010-10-152030-10-15Us
US9233956 No2009-05-042029-05-04Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00327 mg/mLALOGPS
logP5.44ALOGPS
logP5.46ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)7.16ChemAxon
pKa (Strongest Basic)2.91ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area110.86 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity127.51 m3·mol-1ChemAxon
Polarizability49.71 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Gibney GT, Zager JS: Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies. Expert Opin Drug Metab Toxicol. 2013 Jul;9(7):893-9. doi: 10.1517/17425255.2013.794220. Epub 2013 Apr 29. [PubMed:23621583 ]
External Links
ATC CodesL01XE23
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (418 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Abiraterone can be decreased when it is combined with Dabrafenib.
AcenocoumarolThe serum concentration of Acenocoumarol can be decreased when it is combined with Dabrafenib.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Dabrafenib.
AlfuzosinThe serum concentration of Alfuzosin can be decreased when it is combined with Dabrafenib.
AlogliptinThe therapeutic efficacy of Alogliptin can be decreased when used in combination with Dabrafenib.
AlprazolamThe serum concentration of Alprazolam can be decreased when it is combined with Dabrafenib.
Aluminum hydroxideThe serum concentration of Dabrafenib can be decreased when it is combined with Aluminum hydroxide.
AminophyllineThe serum concentration of Aminophylline can be decreased when it is combined with Dabrafenib.
AmiodaroneThe serum concentration of Amiodarone can be decreased when it is combined with Dabrafenib.
AmlodipineThe serum concentration of Amlodipine can be decreased when it is combined with Dabrafenib.
ApixabanThe serum concentration of Apixaban can be decreased when it is combined with Dabrafenib.
ApremilastThe serum concentration of Apremilast can be decreased when it is combined with Dabrafenib.
AprepitantThe serum concentration of Aprepitant can be decreased when it is combined with Dabrafenib.
AripiprazoleThe serum concentration of Aripiprazole can be decreased when it is combined with Dabrafenib.
ArmodafinilThe serum concentration of Armodafinil can be decreased when it is combined with Dabrafenib.
AtazanavirThe serum concentration of Atazanavir can be decreased when it is combined with Dabrafenib.
AtorvastatinThe serum concentration of Atorvastatin can be decreased when it is combined with Dabrafenib.
AvanafilThe serum concentration of Avanafil can be decreased when it is combined with Dabrafenib.
AxitinibThe serum concentration of Axitinib can be decreased when it is combined with Dabrafenib.
BedaquilineThe serum concentration of Bedaquiline can be decreased when it is combined with Dabrafenib.
BenzphetamineThe serum concentration of Benzphetamine can be decreased when it is combined with Dabrafenib.
BisoprololThe serum concentration of Bisoprolol can be decreased when it is combined with Dabrafenib.
BoceprevirThe serum concentration of Boceprevir can be decreased when it is combined with Dabrafenib.
BortezomibThe serum concentration of Bortezomib can be decreased when it is combined with Dabrafenib.
BosutinibThe serum concentration of Bosutinib can be decreased when it is combined with Dabrafenib.
BrexpiprazoleThe serum concentration of Brexpiprazole can be decreased when it is combined with Dabrafenib.
BuprenorphineThe serum concentration of Buprenorphine can be decreased when it is combined with Dabrafenib.
BupropionThe serum concentration of Bupropion can be decreased when it is combined with Dabrafenib.
BuspironeThe serum concentration of Buspirone can be decreased when it is combined with Dabrafenib.
CabazitaxelThe serum concentration of Cabazitaxel can be decreased when it is combined with Dabrafenib.
CabozantinibThe serum concentration of Cabozantinib can be decreased when it is combined with Dabrafenib.
CalcitriolThe serum concentration of Calcitriol can be decreased when it is combined with Dabrafenib.
Calcium carbonateThe serum concentration of Dabrafenib can be decreased when it is combined with Calcium carbonate.
CanagliflozinThe therapeutic efficacy of Canagliflozin can be decreased when used in combination with Dabrafenib.
CarbamazepineThe serum concentration of Carbamazepine can be decreased when it is combined with Dabrafenib.
CarisoprodolThe serum concentration of Carisoprodol can be decreased when it is combined with Dabrafenib.
CelecoxibThe serum concentration of Celecoxib can be decreased when it is combined with Dabrafenib.
CeritinibThe serum concentration of Ceritinib can be decreased when it is combined with Dabrafenib.
ChlordiazepoxideThe serum concentration of Chlordiazepoxide can be decreased when it is combined with Dabrafenib.
ChloroquineThe serum concentration of Chloroquine can be decreased when it is combined with Dabrafenib.
ChlorotrianiseneThe serum concentration of Chlorotrianisene can be decreased when it is combined with Dabrafenib.
ChlorpropamideThe therapeutic efficacy of Chlorpropamide can be decreased when used in combination with Dabrafenib.
CilostazolThe serum concentration of Cilostazol can be decreased when it is combined with Dabrafenib.
CimetidineThe serum concentration of Dabrafenib can be decreased when it is combined with Cimetidine.
CitalopramThe serum concentration of Citalopram can be decreased when it is combined with Dabrafenib.
ClarithromycinThe serum concentration of Clarithromycin can be decreased when it is combined with Dabrafenib.
ClobazamThe serum concentration of Clobazam can be decreased when it is combined with Dabrafenib.
ClomipramineThe serum concentration of Clomipramine can be decreased when it is combined with Dabrafenib.
ClonazepamThe serum concentration of Clonazepam can be decreased when it is combined with Dabrafenib.
ClorazepateThe serum concentration of Clorazepate can be decreased when it is combined with Dabrafenib.
CobicistatThe serum concentration of Cobicistat can be decreased when it is combined with Dabrafenib.
ConivaptanThe serum concentration of Dabrafenib can be increased when it is combined with Conivaptan.
CrizotinibThe serum concentration of Crizotinib can be decreased when it is combined with Dabrafenib.
CyclophosphamideThe serum concentration of Cyclophosphamide can be decreased when it is combined with Dabrafenib.
CyclosporineThe serum concentration of Cyclosporine can be decreased when it is combined with Dabrafenib.
Cyproterone acetateThe serum concentration of Cyproterone acetate can be decreased when it is combined with Dabrafenib.
DaclatasvirThe serum concentration of Daclatasvir can be decreased when it is combined with Dabrafenib.
DantroleneThe serum concentration of Dantrolene can be decreased when it is combined with Dabrafenib.
DapsoneThe serum concentration of Dapsone can be decreased when it is combined with Dabrafenib.
DarifenacinThe serum concentration of Darifenacin can be decreased when it is combined with Dabrafenib.
DarunavirThe serum concentration of Darunavir can be decreased when it is combined with Dabrafenib.
DasatinibThe serum concentration of Dasatinib can be decreased when it is combined with Dabrafenib.
DeferasiroxThe serum concentration of Dabrafenib can be increased when it is combined with Deferasirox.
DelavirdineThe serum concentration of Delavirdine can be decreased when it is combined with Dabrafenib.
DexamethasoneThe serum concentration of Dexamethasone can be decreased when it is combined with Dabrafenib.
DiazepamThe serum concentration of Diazepam can be decreased when it is combined with Dabrafenib.
DienogestThe serum concentration of Dienogest can be decreased when it is combined with Dabrafenib.
DiltiazemThe serum concentration of Diltiazem can be decreased when it is combined with Dabrafenib.
DisopyramideThe serum concentration of Disopyramide can be decreased when it is combined with Dabrafenib.
DocetaxelThe serum concentration of Docetaxel can be decreased when it is combined with Dabrafenib.
DofetilideDabrafenib may increase the QTc-prolonging activities of Dofetilide.
DoxazosinThe serum concentration of Doxazosin can be decreased when it is combined with Dabrafenib.
DoxorubicinThe serum concentration of Doxorubicin can be decreased when it is combined with Dabrafenib.
DronedaroneThe serum concentration of Dronedarone can be decreased when it is combined with Dabrafenib.
EfavirenzThe serum concentration of Efavirenz can be decreased when it is combined with Dabrafenib.
EliglustatThe serum concentration of Eliglustat can be decreased when it is combined with Dabrafenib.
ElvitegravirThe serum concentration of Elvitegravir can be decreased when it is combined with Dabrafenib.
EnzalutamideThe serum concentration of Enzalutamide can be decreased when it is combined with Dabrafenib.
EplerenoneThe serum concentration of Eplerenone can be decreased when it is combined with Dabrafenib.
ErlotinibThe serum concentration of Erlotinib can be decreased when it is combined with Dabrafenib.
ErythromycinThe serum concentration of Erythromycin can be decreased when it is combined with Dabrafenib.
EscitalopramThe serum concentration of Escitalopram can be decreased when it is combined with Dabrafenib.
EsomeprazoleThe serum concentration of Esomeprazole can be decreased when it is combined with Dabrafenib.
EstradiolThe serum concentration of Estradiol can be decreased when it is combined with Dabrafenib.
Estrone sulfateThe serum concentration of Estropipate can be decreased when it is combined with Dabrafenib.
EszopicloneThe serum concentration of Eszopiclone can be decreased when it is combined with Dabrafenib.
EthosuximideThe serum concentration of Ethosuximide can be decreased when it is combined with Dabrafenib.
EtonogestrelThe serum concentration of Etonogestrel can be decreased when it is combined with Dabrafenib.
EtoposideThe serum concentration of Etoposide can be decreased when it is combined with Dabrafenib.
EtravirineThe serum concentration of Etravirine can be decreased when it is combined with Dabrafenib.
EverolimusThe serum concentration of Everolimus can be decreased when it is combined with Dabrafenib.
ExemestaneThe serum concentration of Exemestane can be decreased when it is combined with Dabrafenib.
FamotidineThe serum concentration of Dabrafenib can be decreased when it is combined with Famotidine.
FelbamateThe serum concentration of Felbamate can be decreased when it is combined with Dabrafenib.
FelodipineThe serum concentration of Felodipine can be decreased when it is combined with Dabrafenib.
FentanylThe serum concentration of Fentanyl can be decreased when it is combined with Dabrafenib.
FesoterodineThe serum concentration of Fesoterodine can be decreased when it is combined with Dabrafenib.
FlibanserinThe serum concentration of Flibanserin can be decreased when it is combined with Dabrafenib.
FluconazoleThe metabolism of Dabrafenib can be decreased when combined with Fluconazole.
FlunisolideThe serum concentration of Flunisolide can be decreased when it is combined with Dabrafenib.
FluoxetineThe serum concentration of Fluoxetine can be decreased when it is combined with Dabrafenib.
FlurazepamThe serum concentration of Flurazepam can be decreased when it is combined with Dabrafenib.
FlutamideThe serum concentration of Flutamide can be decreased when it is combined with Dabrafenib.
FosamprenavirThe serum concentration of Fosamprenavir can be decreased when it is combined with Dabrafenib.
FosaprepitantThe serum concentration of Fosaprepitant can be decreased when it is combined with Dabrafenib.
FosphenytoinThe serum concentration of Fosphenytoin can be decreased when it is combined with Dabrafenib.
Fusidic AcidThe serum concentration of Dabrafenib can be increased when it is combined with Fusidic Acid.
GefitinibThe serum concentration of Gefitinib can be decreased when it is combined with Dabrafenib.
GliclazideThe therapeutic efficacy of Gliclazide can be decreased when used in combination with Dabrafenib.
GlimepirideThe therapeutic efficacy of Glimepiride can be decreased when used in combination with Dabrafenib.
GlipizideThe serum concentration of Glipizide can be decreased when it is combined with Dabrafenib.
GliquidoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Dabrafenib.
GlyburideThe therapeutic efficacy of Glyburide can be decreased when used in combination with Dabrafenib.
GoserelinDabrafenib may increase the QTc-prolonging activities of Goserelin.
GuanfacineThe serum concentration of Guanfacine can be decreased when it is combined with Dabrafenib.
HaloperidolThe serum concentration of Haloperidol can be decreased when it is combined with Dabrafenib.
HydrocodoneThe serum concentration of Hydrocodone can be decreased when it is combined with Dabrafenib.
Hydroxyprogesterone caproateThe serum concentration of Hydroxyprogesterone caproate can be decreased when it is combined with Dabrafenib.
IbrutinibThe serum concentration of Ibrutinib can be decreased when it is combined with Dabrafenib.
IdelalisibThe serum concentration of Dabrafenib can be increased when it is combined with Idelalisib.
IfosfamideThe serum concentration of Ifosfamide can be decreased when it is combined with Dabrafenib.
ImatinibThe serum concentration of Imatinib can be decreased when it is combined with Dabrafenib.
ImipramineThe serum concentration of Imipramine can be decreased when it is combined with Dabrafenib.
IndinavirThe serum concentration of Indinavir can be decreased when it is combined with Dabrafenib.
Insulin AspartThe therapeutic efficacy of Insulin Aspart can be decreased when used in combination with Dabrafenib.
Insulin DetemirThe therapeutic efficacy of Insulin Detemir can be decreased when used in combination with Dabrafenib.
Insulin GlargineThe therapeutic efficacy of Insulin Glargine can be decreased when used in combination with Dabrafenib.
Insulin GlulisineThe therapeutic efficacy of Insulin Glulisine can be decreased when used in combination with Dabrafenib.
Insulin HumanThe therapeutic efficacy of Insulin Regular can be decreased when used in combination with Dabrafenib.
Insulin LisproThe therapeutic efficacy of Insulin Lispro can be decreased when used in combination with Dabrafenib.
IrinotecanThe serum concentration of Irinotecan can be decreased when it is combined with Dabrafenib.
IsavuconazoniumThe serum concentration of Isavuconazonium can be decreased when it is combined with Dabrafenib.
IsosorbideThe serum concentration of Isosorbide can be decreased when it is combined with Dabrafenib.
Isosorbide DinitrateThe serum concentration of Isosorbide Dinitrate can be decreased when it is combined with Dabrafenib.
Isosorbide MononitrateThe serum concentration of Isosorbide Mononitrate can be decreased when it is combined with Dabrafenib.
IsradipineThe serum concentration of Isradipine can be decreased when it is combined with Dabrafenib.
ItraconazoleThe serum concentration of Itraconazole can be decreased when it is combined with Dabrafenib.
IvabradineThe serum concentration of Ivabradine can be decreased when it is combined with Dabrafenib.
IvacaftorThe serum concentration of Ivacaftor can be decreased when it is combined with Dabrafenib.
IxabepiloneThe serum concentration of Ixabepilone can be decreased when it is combined with Dabrafenib.
IxazomibThe serum concentration of Ixazomib can be decreased when it is combined with Dabrafenib.
KetamineThe serum concentration of Ketamine can be decreased when it is combined with Dabrafenib.
KetoconazoleThe serum concentration of Ketoconazole can be decreased when it is combined with Dabrafenib.
LansoprazoleThe serum concentration of Lansoprazole can be decreased when it is combined with Dabrafenib.
LapatinibThe serum concentration of Lapatinib can be decreased when it is combined with Dabrafenib.
LeuprolideDabrafenib may increase the QTc-prolonging activities of Leuprolide.
LevonorgestrelThe serum concentration of Levonorgestrel can be decreased when it is combined with Dabrafenib.
LidocaineThe serum concentration of Lidocaine can be decreased when it is combined with Dabrafenib.
LinagliptinThe therapeutic efficacy of Linagliptin can be decreased when used in combination with Dabrafenib.
LomitapideThe serum concentration of Lomitapide can be decreased when it is combined with Dabrafenib.
LosartanThe serum concentration of Losartan can be decreased when it is combined with Dabrafenib.
LovastatinThe serum concentration of Lovastatin can be decreased when it is combined with Dabrafenib.
LuliconazoleThe serum concentration of Dabrafenib can be increased when it is combined with Luliconazole.
LumacaftorThe serum concentration of Dabrafenib can be increased when it is combined with Lumacaftor.
LurasidoneThe serum concentration of Lurasidone can be decreased when it is combined with Dabrafenib.
MacitentanThe serum concentration of MACITENTAN can be decreased when it is combined with Dabrafenib.
Magnesium hydroxideThe serum concentration of Dabrafenib can be decreased when it is combined with Magnesium hydroxide.
Magnesium oxideThe serum concentration of Dabrafenib can be decreased when it is combined with Magnesium oxide.
MaravirocThe serum concentration of Maraviroc can be decreased when it is combined with Dabrafenib.
Medroxyprogesterone AcetateThe serum concentration of Medroxyprogesterone Acetate can be decreased when it is combined with Dabrafenib.
MefloquineThe serum concentration of Mefloquine can be decreased when it is combined with Dabrafenib.
MeloxicamThe serum concentration of Meloxicam can be decreased when it is combined with Dabrafenib.
MetforminThe therapeutic efficacy of Metformin can be decreased when used in combination with Dabrafenib.
MethadoneThe serum concentration of Methadone can be decreased when it is combined with Dabrafenib.
MethsuximideThe serum concentration of Methsuximide can be decreased when it is combined with Dabrafenib.
MidazolamThe serum concentration of Midazolam can be decreased when it is combined with Dabrafenib.
MifepristoneThe serum concentration of Mifepristone can be decreased when it is combined with Dabrafenib.
MirtazapineThe serum concentration of Mirtazapine can be decreased when it is combined with Dabrafenib.
MoclobemideThe serum concentration of Moclobemide can be decreased when it is combined with Dabrafenib.
ModafinilThe serum concentration of Modafinil can be decreased when it is combined with Dabrafenib.
NaloxegolThe serum concentration of Naloxegol can be decreased when it is combined with Dabrafenib.
NateglinideThe serum concentration of Nateglinide can be decreased when it is combined with Dabrafenib.
NefazodoneThe serum concentration of Nefazodone can be decreased when it is combined with Dabrafenib.
NelfinavirThe serum concentration of Nelfinavir can be decreased when it is combined with Dabrafenib.
NevirapineThe serum concentration of Nevirapine can be decreased when it is combined with Dabrafenib.
NicardipineThe serum concentration of Nicardipine can be decreased when it is combined with Dabrafenib.
NifedipineThe serum concentration of Nifedipine can be decreased when it is combined with Dabrafenib.
NilotinibThe serum concentration of Nilotinib can be decreased when it is combined with Dabrafenib.
NilutamideThe serum concentration of Nilutamide can be decreased when it is combined with Dabrafenib.
NimodipineThe serum concentration of Nimodipine can be decreased when it is combined with Dabrafenib.
NisoldipineThe serum concentration of Nisoldipine can be decreased when it is combined with Dabrafenib.
NizatidineThe serum concentration of Dabrafenib can be decreased when it is combined with Nizatidine.
NorethisteroneThe serum concentration of Norethindrone can be decreased when it is combined with Dabrafenib.
OlaparibThe serum concentration of Olaparib can be decreased when it is combined with Dabrafenib.
OmeprazoleThe serum concentration of Omeprazole can be decreased when it is combined with Dabrafenib.
OndansetronThe serum concentration of Ondansetron can be decreased when it is combined with Dabrafenib.
OspemifeneThe serum concentration of Ospemifene can be decreased when it is combined with Dabrafenib.
OxycodoneThe serum concentration of Oxycodone can be decreased when it is combined with Dabrafenib.
PaclitaxelThe serum concentration of Paclitaxel can be decreased when it is combined with Dabrafenib.
PalbociclibThe serum concentration of Palbociclib can be decreased when it is combined with Dabrafenib.
PanobinostatThe serum concentration of Panobinostat can be decreased when it is combined with Dabrafenib.
PantoprazoleThe serum concentration of Pantoprazole can be decreased when it is combined with Dabrafenib.
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Dabrafenib.
PentamidineThe serum concentration of Pentamidine can be decreased when it is combined with Dabrafenib.
PerampanelThe serum concentration of Perampanel can be decreased when it is combined with Dabrafenib.
PhenobarbitalThe serum concentration of Phenobarbital can be decreased when it is combined with Dabrafenib.
PhenytoinThe serum concentration of Phenytoin can be decreased when it is combined with Dabrafenib.
PimozideThe serum concentration of Pimozide can be decreased when it is combined with Dabrafenib.
PioglitazoneThe serum concentration of Pioglitazone can be decreased when it is combined with Dabrafenib.
PipotiazineThe serum concentration of Pipotiazine can be decreased when it is combined with Dabrafenib.
PiroxicamThe serum concentration of Piroxicam can be decreased when it is combined with Dabrafenib.
PraziquantelThe serum concentration of Praziquantel can be decreased when it is combined with Dabrafenib.
PrimaquineThe serum concentration of Primaquine can be decreased when it is combined with Dabrafenib.
ProgesteroneThe serum concentration of Progesterone can be decreased when it is combined with Dabrafenib.
PromethazineThe serum concentration of Promethazine can be decreased when it is combined with Dabrafenib.
QuetiapineThe serum concentration of Quetiapine can be decreased when it is combined with Dabrafenib.
QuinidineThe serum concentration of Quinidine can be decreased when it is combined with Dabrafenib.
QuinineThe serum concentration of Quinine can be decreased when it is combined with Dabrafenib.
RabeprazoleThe serum concentration of Rabeprazole can be decreased when it is combined with Dabrafenib.
RanitidineThe serum concentration of Dabrafenib can be decreased when it is combined with Ranitidine.
RanolazineThe serum concentration of Ranolazine can be decreased when it is combined with Dabrafenib.
RegorafenibThe serum concentration of Regorafenib can be decreased when it is combined with Dabrafenib.
RepaglinideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Dabrafenib.
RifabutinThe serum concentration of Rifabutin can be decreased when it is combined with Dabrafenib.
RilpivirineThe serum concentration of Rilpivirine can be decreased when it is combined with Dabrafenib.
RiociguatThe serum concentration of Riociguat can be decreased when it is combined with Dabrafenib.
RitonavirThe serum concentration of Ritonavir can be decreased when it is combined with Dabrafenib.
RivaroxabanThe serum concentration of Rivaroxaban can be decreased when it is combined with Dabrafenib.
RoflumilastThe serum concentration of Roflumilast can be decreased when it is combined with Dabrafenib.
RolapitantThe serum concentration of Rolapitant can be decreased when it is combined with Dabrafenib.
RosiglitazoneThe serum concentration of Rosiglitazone can be decreased when it is combined with Dabrafenib.
RuxolitinibThe serum concentration of Ruxolitinib can be decreased when it is combined with Dabrafenib.
SaquinavirThe serum concentration of Saquinavir can be decreased when it is combined with Dabrafenib.
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Dabrafenib.
SelegilineThe serum concentration of Selegiline can be decreased when it is combined with Dabrafenib.
SildenafilThe serum concentration of Sildenafil can be decreased when it is combined with Dabrafenib.
SilodosinThe serum concentration of Silodosin can be decreased when it is combined with Dabrafenib.
SimeprevirThe serum concentration of Simeprevir can be decreased when it is combined with Dabrafenib.
SimvastatinThe serum concentration of Simvastatin can be decreased when it is combined with Dabrafenib.
SirolimusThe serum concentration of Sirolimus can be decreased when it is combined with Dabrafenib.
Sodium bicarbonateThe serum concentration of Dabrafenib can be decreased when it is combined with Sodium bicarbonate.
SolifenacinThe serum concentration of Solifenacin can be decreased when it is combined with Dabrafenib.
SonidegibThe serum concentration of Sonidegib can be decreased when it is combined with Dabrafenib.
SpiramycinThe serum concentration of Spiramycin can be decreased when it is combined with Dabrafenib.
St. John's WortThe serum concentration of Dabrafenib can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Dabrafenib can be increased when it is combined with Stiripentol.
SulfadiazineThe serum concentration of Sulfadiazine can be decreased when it is combined with Dabrafenib.
SunitinibThe serum concentration of Sunitinib can be decreased when it is combined with Dabrafenib.
SuvorexantThe serum concentration of Suvorexant can be decreased when it is combined with Dabrafenib.
TacrolimusThe serum concentration of Tacrolimus can be decreased when it is combined with Dabrafenib.
TamoxifenThe serum concentration of Tamoxifen can be decreased when it is combined with Dabrafenib.
TamsulosinThe serum concentration of Tamsulosin can be decreased when it is combined with Dabrafenib.
TasimelteonThe serum concentration of Tasimelteon can be decreased when it is combined with Dabrafenib.
TelaprevirThe serum concentration of Telaprevir can be decreased when it is combined with Dabrafenib.
TelithromycinThe serum concentration of Telithromycin can be decreased when it is combined with Dabrafenib.
TemsirolimusThe serum concentration of Temsirolimus can be decreased when it is combined with Dabrafenib.
TeniposideThe serum concentration of Teniposide can be decreased when it is combined with Dabrafenib.
TetracyclineThe serum concentration of Tetracycline can be decreased when it is combined with Dabrafenib.
TheophyllineThe serum concentration of Theophylline can be decreased when it is combined with Dabrafenib.
TiagabineThe serum concentration of Tiagabine can be decreased when it is combined with Dabrafenib.
TicagrelorThe serum concentration of Ticagrelor can be decreased when it is combined with Dabrafenib.
TiclopidineThe serum concentration of Ticlopidine can be decreased when it is combined with Dabrafenib.
TipranavirThe serum concentration of Tipranavir can be decreased when it is combined with Dabrafenib.
TofacitinibThe serum concentration of Tofacitinib can be decreased when it is combined with Dabrafenib.
TolbutamideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Dabrafenib.
TolterodineThe serum concentration of Tolterodine can be decreased when it is combined with Dabrafenib.
TolvaptanThe serum concentration of Tolvaptan can be decreased when it is combined with Dabrafenib.
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Dabrafenib.
TorasemideThe serum concentration of Torasemide can be decreased when it is combined with Dabrafenib.
ToremifeneThe serum concentration of Toremifene can be decreased when it is combined with Dabrafenib.
TrabectedinThe serum concentration of Trabectedin can be decreased when it is combined with Dabrafenib.
TramadolThe serum concentration of Tramadol can be decreased when it is combined with Dabrafenib.
TrametinibThe risk or severity of adverse effects can be increased when Trametinib is combined with Dabrafenib.
TrazodoneThe serum concentration of Trazodone can be decreased when it is combined with Dabrafenib.
TretinoinThe serum concentration of Tretinoin can be decreased when it is combined with Dabrafenib.
TriazolamThe serum concentration of Triazolam can be decreased when it is combined with Dabrafenib.
TrimethoprimThe serum concentration of Trimethoprim can be decreased when it is combined with Dabrafenib.
TrimipramineThe serum concentration of Trimipramine can be decreased when it is combined with Dabrafenib.
UlipristalThe serum concentration of Ulipristal can be decreased when it is combined with Dabrafenib.
VandetanibThe serum concentration of Vandetanib can be decreased when it is combined with Dabrafenib.
VemurafenibThe serum concentration of Vemurafenib can be decreased when it is combined with Dabrafenib.
VenlafaxineThe serum concentration of Venlafaxine can be decreased when it is combined with Dabrafenib.
VerapamilThe serum concentration of Verapamil can be decreased when it is combined with Dabrafenib.
VilazodoneThe serum concentration of Vilazodone can be decreased when it is combined with Dabrafenib.
VildagliptinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Dabrafenib.
VinblastineThe serum concentration of Vinblastine can be decreased when it is combined with Dabrafenib.
VincristineThe serum concentration of Vincristine can be decreased when it is combined with Dabrafenib.
VinorelbineThe serum concentration of Vinorelbine can be decreased when it is combined with Dabrafenib.
VoriconazoleThe serum concentration of Voriconazole can be decreased when it is combined with Dabrafenib.
VortioxetineThe serum concentration of Vortioxetine can be decreased when it is combined with Dabrafenib.
WarfarinThe serum concentration of Warfarin can be decreased when it is combined with Dabrafenib.
ZafirlukastThe serum concentration of Zafirlukast can be decreased when it is combined with Dabrafenib.
ZolpidemThe serum concentration of Zolpidem can be decreased when it is combined with Dabrafenib.
ZonisamideThe serum concentration of Zonisamide can be decreased when it is combined with Dabrafenib.
ZopicloneThe serum concentration of Zopiclone can be decreased when it is combined with Dabrafenib.
Food Interactions
  • When taken with a fatty meal, Cmax and AUC decreased. Tmax is also prolonged compared to the fasted condition.

Targets

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
References
  1. Gibney GT, Zager JS: Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies. Expert Opin Drug Metab Toxicol. 2013 Jul;9(7):893-9. doi: 10.1517/17425255.2013.794220. Epub 2013 Apr 29. [PubMed:23621583 ]
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
References
  1. FDA label
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Protein serine/threonine kinase activity
Specific Function:
Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. Phosphorylates HDAC4, HDAC5, PPME1, SREBF1, CRTC1/TORC1 and CRTC2/TORC2. Acts as a tumor suppressor and plays a key role in p53/TP53-dependent anoikis, a type of apoptosis triggered by cell detachment: r...
Gene Name:
SIK1
Uniprot ID:
P57059
Molecular Weight:
84901.25 Da
References
  1. FDA label
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Protein serine/threonine kinase activity
Specific Function:
Protein kinase which plays an important role in the G2/M checkpoint response to DNA damage. Controls degradation of CDC25A by directly phosphorylating it on residues whose phosphorylation is required for BTRC-mediated polyubiquitination and degradation.
Gene Name:
NEK11
Uniprot ID:
Q8NG66
Molecular Weight:
74191.62 Da
References
  1. FDA label
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Zinc ion binding
Specific Function:
Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways. Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop. LIMK1 subsequently phosphorylates and inactivates the actin binding/depo...
Gene Name:
LIMK1
Uniprot ID:
P53667
Molecular Weight:
72584.4 Da
References
  1. FDA label

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinducer
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
References
  1. FDA label
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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
References
  1. FDA label

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
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
Molecular Weight:
141477.255 Da
References
  1. Mittapalli RK, Vaidhyanathan S, Dudek AZ, Elmquist WF: Mechanisms limiting distribution of the threonine-protein kinase B-RaF(V600E) inhibitor dabrafenib to the brain: implications for the treatment of melanoma brain metastases. J Pharmacol Exp Ther. 2013 Mar;344(3):655-64. doi: 10.1124/jpet.112.201475. Epub 2012 Dec 17. [PubMed:23249624 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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
References
  1. Mittapalli RK, Vaidhyanathan S, Dudek AZ, Elmquist WF: Mechanisms limiting distribution of the threonine-protein kinase B-RaF(V600E) inhibitor dabrafenib to the brain: implications for the treatment of melanoma brain metastases. J Pharmacol Exp Ther. 2013 Mar;344(3):655-64. doi: 10.1124/jpet.112.201475. Epub 2012 Dec 17. [PubMed:23249624 ]
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, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular Weight:
76447.99 Da
References
  1. FDA label
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 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B3
Uniprot ID:
Q9NPD5
Molecular Weight:
77402.175 Da
References
  1. FDA label
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 molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
References
  1. FDA label
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, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
  1. FDA label
Comments
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Drug created on June 24, 2013 15:54 / Updated on May 30, 2016 02:16