General
Preferred name
DABRAFENIB
Synonyms
GSK2118436 ()
GSK2118436A, GSK2118436B, Dabrafenib Mesylate ()
GSK2118436A ()
DABRAFENIB MESYLATE ()
Dabrafenib (GSK2118436A) ()
GSK2118436B ()
TAFINLAR ()
CT-DABR ()
Dabrafenib (Mesylate) ()
GSK-2118436 ()
GSK-2118436A ()
GSK2118436 Mesylate ()
GSK 2118436B ()
Dabrafenib (GSK2118436) ()
Gsk2118436 ()
GSK-2118436B ()
Methane Sulfonate Salt ()
GSK-2118436B METHANESULFONATE SALT ()
GSK-2118436 METHANESULFONATE SALT ()
GSK2118436B, METHANE SULFONATE SALT ()
Dabrafenib mesilate ()
GSK-2118436B MESYLATE ()
Dabrafenib-d9 ()
Dabrafenib (mesylate) ()
P&D ID
PD003542
CAS
1195765-45-7
1195768-06-9
1423119-98-5
Tags
available
drug
Approved by
PMDA
EMA
FDA
First approval
2013
Drug Status
investigational
approved
Drug indication
Melanoma
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS Dabrafenib causes an inhibition of phosphorylated extracellular signal-regulated kinase (ERK). This indicates a decrease in cell proliferation. Furthermore, within 24 hours of administration, downstream mediators of the MAPK pathway were inhibited [FDA label].; ; The melanoma approval for use with Mekinist is based on results from COMBI-AD, a Phase III study of 870 patients with Stage III BRAF V600E/K mutation-positive melanoma treated with Tafinlar + Mekinist after complete surgical resection. Patients received doses of Tafinlar (150 mg BID) + Mekinist (2 mg QD) combination (n = 438) or matching placebos (n = 432). After a median follow-up of 2.8 years, the primary endpoint of relapse-free survival (RFS) was met [L2714]. Thus, Tafinlar in combination with Mekinist treats melanoma. ; ; In the case of thyroid cancer, Dabrafenib plus Trametinib is the first regimen demonstrated to have potent clinical activity in BRAF V600E–mutated anaplastic thyroid cancer and is well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease [L2723].
MOA Dabrafenib is an orally bioavailable inhibitor of B-raf (BRAF) protein with antineoplastic activity. Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. B-raf belongs to the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/Extracellular Signal-regulated Kinases signaling pathway, which may be constitutively activated due to BRAF gene mutations [FDA label].;
INDICATION Tafinlar is a kinase inhibitor that was initially indicated as a single agent for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test [FDA label].; ; Tafinlar in combination with [DB08911] is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. The use in combination is based on the demonstration of durable response rate. Improvement in disease-related symptoms or overall survival has not been demonstrated for Tafinlar in combination with trametinib [FDA label].; ; In May 2018, Tafinlar (dabrafenib) and Mekinist ([DB08911]) have been approved in combination to treat anaplastic thyroid cancer caused by an abnormal BRAF V600E gene [L2712].
DESCRIPTION Dabrafenib is a Type-1.5 kinase inhibitor. (GtoPdb)
TOXICITY LD50 in rats is > 2000 mg/kg [MSDS].; ; ; The most common side effects of Daretinib (Tafinlar) as a single agent include: hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, and palmar-plantar erythrodysesthesia syndrome [FDA label].; ; The most common adverse reactions (≥20%) for Tafinlar in combination with [DB08911] are pyrexia, chills, fatigue, rash, nausea, vomiting, diarrhea, abdominal pain, peripheral edema, cough, headache, arthralgia, night sweats, decreased appetite, constipation, and myalgia [FDA label].; ; The following is a list of toxicities that may occur with the combination of Daretinib and [DB08911]:; ; **New primary malignancies**: These may occur when Tafinlar is administered as a single agent or in combination with [DB08911]. Monitor patients for new malignancies prior to initiation of therapy, while on therapy, and following discontinuation of TAFINLAR or the combination therapy. Tumor Promotion in BRAF Wild-Type Melanoma: Increased cell proliferation can occur with BRAF inhibitors [FDA label].; ; **Hemorrhage:** Major hemorrhagic events can occur in patients receiving TAFINLAR in combination with trametinib. Monitor for signs and symptoms of bleeding [FDA label]. ; ; **Venous Thromboembolism**: Deep vein thrombosis and pulmonary embolism can occur in patients receiving the drug combination [FDA label].; ; **Cardiomyopathy **: Assess LVEF before treatment with TAFINLAR in combination with trametinib, after one month of treatment, then every 2 to 3 months thereafter [FDA label]. ; ; **Ocular toxicities**: Perform an ophthalmologic evaluation for any visual disturbances [FDA label]. ; ; **Serious Febrile Reactions:** Incidence and severity of pyrexia are increased with TAFINLAR in combination with trametinib [FDA label]. ; ; **Serious Skin Toxicity:** Monitor for skin toxicities and for secondary infections. Discontinue for intolerable Grade 2, or Grade 3 or 4 rash not improving within 3 weeks despite the interruption of TAFINLAR [FDA label]. ; ; **Hyperglycemia:** Monitor serum glucose levels in patients with pre-existing diabetes or hyperglycemia [FDA label]. ; ; **Glucose-6-Phosphate Dehydrogenase Deficiency**: Closely monitor for hemolytic anemia [FDA label]. ; ; **Embryofetal Toxicity**: Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus. TAFINLAR may render hormonal contraceptives less effective and an alternative method of contraception should be used [FDA label].;
DESCRIPTION Dabrafenib is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. (PKIDB)
DESCRIPTION inhibitor of BRAF (Informer Set)
DESCRIPTION Influenza virus neuraminidase inhibitor; antiviral prodrug (Tocris Bioactive Compound Library)
Cell lines
4
Organisms
0
Compound Sets
31
AdooQ Bioactive Compound Library
A11381
A15059
Cayman Chemical Bioactives
16989
35251
28797
ChEMBL Approved Drugs
CHEMBL2028663
CHEMBL2105729
ChEMBL Drugs
CHEMBL2028663
CHEMBL2105729
Clinical kinase drugs
Concise Guide to Pharmacology 2017/18
6494
Concise Guide to Pharmacology 2019/20
6494
Concise Guide to Pharmacology 2021/22
6494
Concise Guide to Pharmacology 2023/24
6494
Drug Repurposing Hub
DrugBank
DB08912
DrugBank Approved Drugs
DB08912
DrugCentral
4801
DrugCentral Approved Drugs
4801
DrugMAP
DMX6OE3
DrugMAP Approved Drugs
DMX6OE3
EU-OPENSCREEN Bioactive Compound Library
EOS100662
Guide to Pharmacology
6494
Informer Set
687954
LINCS compound set
10284-101
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL2028663
LSP-OptimalKinase library (Laboratory of Systems Pharmacology)
CHEMBL2028663
MedChem Express Bioactive Compound Library
HY-14660
HY-14660A
NCATS Inxight Approved Drugs
QGP4HA4G1B
NIH Approved Oncology Drugs
PKIDB
ReFrame library
Selleckchem Bioactive Compound Library
dabrafenib-gsk2118436
dabrafenib-mesylate
TargetMol Bioactive Compound Library
T1903
Tocris Bioactive Compound Library
7223
Welcome Trust Cancer Drugs
1373
External IDs
58
Properties
(calculated by RDKit )
Molecular Weight
519.1
Hydrogen Bond Acceptors
7
Hydrogen Bond Donors
2
Rotatable Bonds
5
Ring Count
4
Aromatic Ring Count
4
cLogP
5.36
TPSA
110.86
Fraction CSP3
0.17
Chiral centers
0.0
Largest ring
6.0
QED
0.37
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
ERK MAPK signaling
MAPK
MAPK/ERK Pathway
Target
BRAF
b-RAF
B-Raf (V600E)
c-Raf
BRAF, LIMK1, NEK11, RAF1, SIK1
RAF1
SIK1
NEK11
LIMK1
Compound status
clinical
Primary Target
Raf Kinases
MOA
Raf
Inhibitor
Raf inhibitor
Indication
melanoma
Source data