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Details

Stereochemistry ACHIRAL
Molecular Formula C23H20F3N5O2S2
Molecular Weight 519.562
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DABRAFENIB

SMILES

CC(C)(C)C1=NC(=C(S1)C2=NC(N)=NC=C2)C3=CC=CC(NS(=O)(=O)C4=C(F)C=CC=C4F)=C3F

InChI

InChIKey=BFSMGDJOXZAERB-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C23H20F3N5O2S2
Molecular Weight 519.562
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Dabrafenib is a selective, orally bioavailable inhibitor of Mutant BRAF protein kinase with potential antineoplastic activity. Dabrafenib inhibits 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. BRAF belongs to the the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations. Mutations in BRAF are associated with increased growth and proliferation of cancer cells. By inhibiting BRAF kinase dabrafenib negatively regulates the proliferation of tumor cells which contain a mutated BRAF gene. Dabrafenib (in combination with trametinib or alone) is indicated for the treatment of unresectable or metastatic melanoma with BRAF V600E mutation

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.2 nM [IC50]
Conditions
PubMed

PubMed

TitleDatePubMed
Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies.
2013 Jul
BRAF inhibitor activity in V600R metastatic melanoma.
2013 Mar
Patents

Sample Use Guides

In Vivo Use Guide
The recommended dosage regimens are: 150 mg orally taken twice daily, approximately 12 hours apart, as a single agent or 150 mg orally taken twice daily, approximately 12 hours apart, in combination with trametinib 2 mg orally taken once daily.
Route of Administration: Oral
In Vitro Use Guide
A375, SK-MEL-28, WM239 and SK-MEL-5 cells with 2.5, 5 and 10 nM dabrafenib for 72 hours. Dabrafenib treatment induced massive Mcl-1 expression at all the three concentrations. The IC50 of dabrafenib in A375, SK-MEL-28 and WM-239 was 5nM, 2nM and 6nM respectively. In dabrafenib resistant A375, SK-MEL-28 and WM-239 cells, which were denoted as A375-DR, SK-MEL-28-DR and WM-239-DR that were incubated with up to 300 nM inhibitor concentrations the IC50s were greater than 100 nM indicating more than 30-fold resistance.
Substance Class Chemical
Created
by admin
on Mon Oct 21 23:30:53 UTC 2019
Edited
by admin
on Mon Oct 21 23:30:53 UTC 2019
Record UNII
QGP4HA4G1B
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DABRAFENIB
DASH   INN   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
GSK-2118436A
Code English
DABRAFENIB [MI]
Common Name English
GSK2118436A
Code English
GSK2118436
Common Name English
GSK-2118436
Code English
DABRAFENIB [USAN]
Common Name English
DABRAFENIB [VANDF]
Common Name English
BENZENESULFONAMIDE, N-(3-(5-(2-AMINO-4-PYRIMIDINYL)-2-(1,1-DIMETHYLETHYL)-4-THIAZOLYL)-2-FLUOROPHENYL)-2,6-DIFLUORO-
Systematic Name English
DABRAFENIB [WHO-DD]
Common Name English
N-(3-(5-(2-AMINOPYRIMIDIN-4-YL)-2-TERT-BUTYL-1,3-THIAZOL-4-YL)-2-FLUOROPHENYL)-2,6-DIFLUOROBENZENESULFONAMIDE
Systematic Name English
DABRAFENIB [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 521616
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
WHO-ATC L01XE23
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
FDA ORPHAN DRUG 506415
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
NCI_THESAURUS C155322
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
FDA ORPHAN DRUG 495915
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
EMA ASSESSMENT REPORTS TAFINLAR (AUTHORIZED: MELANOMA)
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
WHO-VATC QL01XE23
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
FDA ORPHAN DRUG 376812
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
FDA ORPHAN DRUG 329610
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
FDA ORPHAN DRUG 448214
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
NDF-RT N0000175605
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
Code System Code Type Description
NDF-RT
N0000190108
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY Organic Anion Transporting Polypeptide 1B3 Inhibitors [MoA]
MERCK INDEX
M11719
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY
CAS
1195765-45-7
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY
NDF-RT
N0000185506
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY Cytochrome P450 3A4 Inducers [MoA]
NDF-RT
N0000190107
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY Organic Anion Transporting Polypeptide 1B1 Inhibitors [MoA]
ChEMBL
CHEMBL2028663
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY
NDF-RT
N0000185507
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY Cytochrome P450 2C9 Inducers [MoA]
EVMPD
SUB45696
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY
INN
9458
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY
NDF-RT
N0000185607
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY Cytochrome P450 2C19 Inducers [MoA]
NDF-RT
N0000187064
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY Cytochrome P450 2B6 Inducers [MoA]
PUBCHEM
44462760
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY
NDF-RT
N0000190110
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY Organic Anion Transporter 1 Inhibitors [MoA]
IUPHAR
6494
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY
NDF-RT
N0000187063
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY Cytochrome P450 2C8 Inducers [MoA]
NCI_THESAURUS
C82386
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY
LactMed
1195765-45-7
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY
NDF-RT
N0000190113
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY Breast Cancer Resistance Protein Inhibitors [MoA]
EPA CompTox
1195765-45-7
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY
WIKIPEDIA
Dabrafenib
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY
RXCUI
1424911
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY RxNorm
NDF-RT
N0000190111
Created by admin on Mon Oct 21 23:30:54 UTC 2019 , Edited by admin on Mon Oct 21 23:30:54 UTC 2019
PRIMARY Organic Anion Transporter 3 Inhibitors [MoA]
Related Record Type Details
TRANSPORTER -> INHIBITOR
IC50
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
BINDING
TRANSPORTER -> NON-INHIBITOR
TRANSPORTER -> INHIBITOR
[i}/IC50= 2.03; CMAX=2.84
IC50
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
METABOLIC ENZYME -> INDUCER
Related Record Type Details
METABOLITE -> PARENT
URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC