Dabrafenib

Identification

Summary

Dabrafenib is a kinase inhibitor used to treat patients with specific types of melanoma, non-small cell lung cancer, and thyroid cancer.

Brand Names

Tafinlar

Generic Name

Dabrafenib

DrugBank Accession Number

DB08912

Background

Dabrafenib mesylate (Tafinlar) is a reversible ATP-competitive kinase inhibitor and targets the MAPK pathway. It was approved on May 29, 2013, for the treatment of melanoma with V600E or V6000K mutation.²⁰ It was also used for metastatic non-small cell lung cancer with the same mutation.²⁰

In May 2018, Tafinlar (dabrafenib), in combination with Mekinist (Trametinib), was approved to treat anaplastic thyroid cancer caused by an abnormal BRAF V600E gene.²⁰

Type

Small Molecule

Groups

Approved, Investigational

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Dabrafenib (DB08912)

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Weight

Average: 519.562
Monoisotopic: 519.101050904

Chemical Formula

C₂₃H₂₀F₃N₅O₂S₂

Synonyms

• Dabrafenib

External IDs

• GSK-2118436
• GSK-2118436A
• GSK2118436
• GSK2118436A

Pharmacology

Indication

As monotherapy, dabrafenib is indicated to treat unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.²⁰

In combination with trametinib, dabrafenib is indicated to treat for:

• the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test.²⁰
• the adjuvant treatment of melanoma with BRAF V600E or V600K mutations and involvement of lymph node(s), following complete resection.²⁰
• the treatment of metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation.²⁰
• the treatment of locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation and with no satisfactory locoregional treatment options.²⁰
• treatment of adult and pediatric patients six years and older with unresectable or metastatic solid tumours with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on the overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).²³
• the treatment of pediatric patients one year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy.²³

Dabrafenib has limitations of use: it is neither indicated for treating patients with colorectal cancer because of known intrinsic resistance to BRAF inhibition nor wild-type BRAF solid tumours.²³

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Associated Conditions

• Locally Advanced Anaplastic Thyroid Cancer
• Low-Grade Glioma
• Melanoma
• Metastatic Anaplastic Thyroid Cancer
• Metastatic Melanoma
• Metastatic Non-Small Cell Lung Cancer
• Metastatic Solid Tumours
• Unresectable Melanoma
• Unresectable Solid Tumor

Contraindications & Blackbox Warnings

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Pharmacodynamics

Dabrafenib is a kinase inhibitor that is mainly used to target BRAF V600E mutation in multiple types of cancer. Although dabrafenib and trametinib both inhibit the RAS/RAF/MEK/ERK pathway, they inhibit different effectors of the pathway, thus increasing response rate and mitigating resistance without cumulative toxicity.¹¹

The melanoma approval for use with trametinib 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 dabrafenib + trametinib after complete surgical resection. Patients received doses of dabrafenib (150 mg BID) + trametinib (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.¹⁶

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.¹⁹

Mechanism of action

Dabrafenib is a competitive and selective BRAF inhibitor by binding to its ATP pocket.^20,5 Although dabrafenib can inhibit wild-type BRAF, it has a higher affinity for mutant forms of BRAF, including BRAF V600E, BRAF V600K, and BRAF V600D.²⁰ BRAF is a serine/threonine protein kinase and is involved in activating the RAS/RAF/MEK/ERK or MAPK pathway, a pathway that is implicated in cell cycle progression, cell proliferation, and arresting apoptosis.^6,7,8,9Therefore, constitutive active mutation of BRAF such as BRAF V600E is frequently observed in many types of cancer, including melanoma, lung cancer, and colon cancer.¹⁰

Target	Actions	Organism
ASerine/threonine-protein kinase B-raf	inhibitor	Humans
ARAF proto-oncogene serine/threonine-protein kinase	inhibitor	Humans
USerine/threonine-protein kinase SIK1	inhibitor	Humans
USerine/threonine-protein kinase Nek11	inhibitor	Humans
ULIM domain kinase 1	inhibitor	Humans

Absorption

After oral administration, the median time to achieve peak plasma concentration (Tmax) is 2 hours.²⁰ Mean absolute bioavailability of oral dabrafenib is 95%.²⁰ Following a single dose, dabrafenib exposure (Cmax and AUC) increased in a dose-proportional manner across the dose range of 12 mg to 300 mg, but the increase was less than dose-proportional after repeat twice-daily dosing.²⁰ After repeated twice-daily dosing of 150 mg, the mean accumulation ratio was 0.73, and the inter-subject variability (CV%) of AUC at steady-state was 38%.²⁰

Volume of distribution

The apparent volume of distribution (Vc/F) is 70.3 L.²⁰Distribution to the brain is restricted because dabrafenib is a substrate and undergoes efflux by P-glycoprotein and breast cancer resistance protein.²

Protein binding

Dabrafenib is 99.7% bound to human plasma proteins.²⁰

Metabolism

The metabolism of dabrafenib is primarily mediated by CYP2C8 and CYP3A4 to form hydroxy-dabrafenib. Hydroxy-dabrafenib is further oxidized via CYP3A4 to form carboxy-dabrafenib and subsequently excreted in bile and urine. Carboxy-dabrafenib is decarboxylated to form desmethyl-dabrafenib; desmethyl-dabrafenib may be reabsorbed from the gut. Desmethyl-dabrafenib is further metabolized by CYP3A4 to oxidative metabolites.²⁰

Hover over products below to view reaction partners

• Dabrafenib
  • Hydroxy-dabrafenib
    • Carboxy-dabrafenib
      • Desmethyl-dabrafenib
        • M30-Dabrafenib
        • M31-Dabrafenib

Route of elimination

Fecal excretion is the major route of elimination accounting for 71% of radioactive dose while urinary excretion accounted for 23% of total radioactivity as metabolites only.²⁰

Half-life

The mean terminal half-life of dabrafenib is 8 hours after oral administration. Hydroxy-dabrafenib's terminal half-life (10 hours) parallels that of dabrafenib while the carboxy- and desmethyl-dabrafenib metabolites exhibit longer half-lives (21 to 22 hours).²⁰

Clearance

The clearance of dabrafenib is 17.0 L/h after single dosing and 34.4 L/h after 2 weeks of twice-daily dosing.²⁰

Adverse Effects

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Toxicity

Carcinogenicity studies with dabrafenib have not been conducted. Dabrafenib increased the risk of cutaneous squamous cell carcinomas in patients in clinical trials.²⁰

Dabrafenib was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay and was not clastogenic in an in vivo rat bone marrow micronucleus test.²⁰

In a combined female fertility and embryo-fetal development study in rats, a reduction in fertility was noted at doses greater than or equal to 20 mg/kg/day (equivalent to the human exposure at the recommended dose based on AUC). A reduction in the number of ovarian corpora lutea was noted in pregnant females at 300 mg/kg/day (which is approximately three times the human exposure at the recommended dose based on AUC).²⁰

Male fertility studies with dabrafenib have not been conducted; however, in repeat-dose studies, testicular degeneration/depletion was seen in rats and dogs at doses equivalent to and three times the human exposure at the recommended dose based on AUC, respectively.²⁰

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Interacting Gene/Enzyme	Allele name	Genotype(s)	Defining Change(s)	Type(s)	Description	Details
Glucose-6-phosphate 1-dehydrogenase	Villeurbanne	Not Available	1000_1002delACC	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Torun	Not Available	1006A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Sunderland	Not Available	105_107delCAT	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Iwatsuki	Not Available	1081G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Serres	Not Available	1082C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Tondela	Not Available	1084_1101delCTGAACGAGCGCAAGGCC	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Loma Linda	Not Available	1089C->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Aachen	Not Available	1089C->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Tenri	Not Available	1096A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Montpellier	Not Available	1132G>A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Calvo Mackenna	Not Available	1138A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Riley	Not Available	1139T->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Olomouc	Not Available	1141T->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Tomah	Not Available	1153T->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Lynwood	Not Available	1154G->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Madrid	Not Available	1155C->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Iowa, Walter Reed, Springfield	Not Available	1156A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Beverly Hills, Genova, Iwate, Niigata, Yamaguchi	Not Available	1160G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Hartford	Not Available	1162A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Praha	Not Available	1166A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Krakow	Not Available	1175T>C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Wisconsin	Not Available	1177C->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Nashville, Anaheim, Portici	Not Available	1178G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Alhambra	Not Available	1180G->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Bari	Not Available	1187C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Puerto Limon	Not Available	1192G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Covao do Lobo	Not Available	1205C>A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Clinic	Not Available	1215G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Utrecht	Not Available	1225C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Suwalki	Not Available	1226C->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Riverside	Not Available	1228G->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Japan, Shinagawa	Not Available	1229G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Kawasaki	Not Available	1229G->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Munich	Not Available	1231A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Georgia	Not Available	1284C->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Sumare	Not Available	1292T->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Telti/Kobe	Not Available	1318C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Santiago de Cuba, Morioka	Not Available	1339G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Harima	Not Available	1358T->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Figuera da Foz	Not Available	1366G->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Amiens	Not Available	1367A>T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Bangkok Noi	Not Available	1376G->T, 1502T->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Fukaya	Not Available	1462G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Campinas	Not Available	1463G->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Buenos Aires	Not Available	1465C>T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Arakawa	Not Available	1466C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Brighton	Not Available	1488_1490delGAA	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Kozukata	Not Available	159G->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Amsterdam	Not Available	180_182delTCT	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	No name	Not Available	202G->A, 376A->G, 1264C>G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Swansea	Not Available	224T->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Urayasu	Not Available	281_283delAGA	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Vancouver	Not Available	317C->G544C->T592C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Mt Sinai	Not Available	376A->G, 1159C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Plymouth	Not Available	488G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Volendam	Not Available	514C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Shinshu	Not Available	527A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Chikugo	Not Available	535A->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Tsukui	Not Available	561_563delCTC	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Pedoplis-Ckaro	Not Available	573C>G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Santiago	Not Available	593G->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Minnesota, Marion, Gastonia, LeJeune	Not Available	637G->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Cincinnati	Not Available	637G->T, 1037A->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Harilaou	Not Available	648T->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	North Dallas	Not Available	683_685delACA	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Asahikawa	Not Available	695G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Durham	Not Available	713A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Stonybrook	Not Available	724_729delGGCACT	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Wayne	Not Available	769C->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Aveiro	Not Available	806G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Cleveland Corum	Not Available	820G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Lille	Not Available	821A>T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Bangkok	Not Available	825G>C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Sugao	Not Available	826C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	La Jolla	Not Available	832T->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Wexham	Not Available	833C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Piotrkow	Not Available	851T>C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	West Virginia	Not Available	910G->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Omiya	Not Available	921G->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Nara	Not Available	953_976delCCACCAAAGGGTACCTGGAC GACC	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Manhattan	Not Available	962G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Rehevot	Not Available	964T->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Honiara	Not Available	99A->G / 1360C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Tokyo, Fukushima	Not Available	1246G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Chatham	Not Available	1003G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Fushan	Not Available	1004C->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Partenope	Not Available	1052G->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Ierapetra	Not Available	1057C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Anadia	Not Available	1193A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Abeno	Not Available	1220A->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Surabaya	Not Available	1291G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Pawnee	Not Available	1316G->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	S. Antioco	Not Available	1342A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Cassano	Not Available	1347G->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Hermoupolis	Not Available	1347G->C / 1360C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Union,Maewo, Chinese-2, Kalo	Not Available	1360C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Andalus	Not Available	1361G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Cosenza	Not Available	1376G->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Canton, Taiwan- Hakka, Gifu-like, Agrigento-like	Not Available	1376G->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Flores	Not Available	1387C->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Kaiping, Anant, Dhon, Sapporo-like, Wosera	Not Available	1388G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Kamogawa	Not Available	169C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Costanzo	Not Available	179T>C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Amazonia	Not Available	185C->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Songklanagarind	Not Available	196T->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Hechi	Not Available	202G->A / 871G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Namouru	Not Available	208T->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Bao Loc	Not Available	352T>C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Crispim	Not Available	375G->T, 379G->T383T->C384C>T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Acrokorinthos	Not Available	376A->G / 463C->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Santa Maria	Not Available	376A->G / 542A->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Ananindeua	Not Available	376A->G / 871G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Vanua Lava	Not Available	383T->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Valladolid	Not Available	406C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Belem	Not Available	409C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Liuzhou	Not Available	442G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Shenzen	Not Available	473G>A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Taipei “Chinese- 3”	Not Available	493A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Toledo	Not Available	496C>T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Naone	Not Available	497G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Nankang	Not Available	517T->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Miaoli	Not Available	519C->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Mediterranean, Dallas, Panama‚ Sassari, Cagliari, Birmingham	Not Available	563C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Coimbra Shunde	Not Available	592C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Nilgiri	Not Available	593G>A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Radlowo	Not Available	679C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Roubaix	Not Available	811G>C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Haikou	Not Available	835A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Chinese-1	Not Available	835A->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Mizushima	Not Available	848A>G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Osaka	Not Available	853C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Viangchan, Jammu	Not Available	871G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Seoul	Not Available	916G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Ludhiana	Not Available	929G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Farroupilha	Not Available	977C->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Chinese-5	Not Available	1024C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Rignano	Not Available	130G>A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Orissa	Not Available	131C->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	G6PDNice	Not Available	1380G>C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Kamiube, Keelung	Not Available	1387C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Neapolis	Not Available	1400C->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Aures	Not Available	143T->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Split	Not Available	1442C->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Kambos	Not Available	148C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Palestrina	Not Available	170G>A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Metaponto	Not Available	172G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Musashino	Not Available	185C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Asahi	Not Available	202G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	A- (202), Ferrara I	Not Available	202G->A / 376A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Murcia Oristano	Not Available	209A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Ube Konan	Not Available	241C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Lagosanto	Not Available	242G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Guangzhou	Not Available	274C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Hammersmith	Not Available	323T->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Sinnai	Not Available	34G->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	A- (680)	Not Available	376A->G / 680G->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	A- (968), Betica,Selma, Guantanamo	Not Available	376A->G / 968T->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Salerno Pyrgos	Not Available	383T>G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Quing Yan	Not Available	392G->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Lages	Not Available	40G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Ilesha	Not Available	466G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Mahidol	Not Available	487G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Malaga	Not Available	542A->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Sibari	Not Available	634A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Mexico City	Not Available	680G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Nanning	Not Available	703C->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Seattle, Lodi, Modena, Ferrara II, Athens-like	Not Available	844G->C	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Bajo Maumere	Not Available	844G->T	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Montalbano	Not Available	854G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Kalyan-Kerala, Jamnaga, Rohini	Not Available	949G->A	ADR Inferred	Increased risk of hemolytic anemia.	Details
Glucose-6-phosphate 1-dehydrogenase	Gaohe	Not Available	95A->G	ADR Inferred	Increased risk of hemolytic anemia.	Details

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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1,2-Benzodiazepine	The serum concentration of 1,2-Benzodiazepine can be decreased when it is combined with Dabrafenib.
Abacavir	The metabolism of Abacavir can be decreased when combined with Dabrafenib.
Abametapir	The serum concentration of Dabrafenib can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Dabrafenib can be increased when combined with Abatacept.
Abemaciclib	The serum concentration of Abemaciclib can be decreased when it is combined with Dabrafenib.
Abiraterone	The serum concentration of Abiraterone can be decreased when it is combined with Dabrafenib.
Abrocitinib	The metabolism of Abrocitinib can be increased when combined with Dabrafenib.
Acalabrutinib	The serum concentration of Acalabrutinib can be decreased when it is combined with Dabrafenib.
Acamprosate	The excretion of Acamprosate can be decreased when combined with Dabrafenib.
Acarbose	The therapeutic efficacy of Acarbose can be decreased when used in combination with Dabrafenib.

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Food Interactions

• Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum levels of dabrafenib.
• Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce serum levels of dabrafenib.
• Do not take with or immediately after a high-fat meal. Dabrafenib's bioavailability is reduced when taken with a high-fat meal.
• Take on an empty stomach. Take dabrafenib at least one hour before or two hours after a meal.

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Dabrafenib mesylate	B6DC89I63E	1195768-06-9	YKGMKSIHIVVYKY-UHFFFAOYSA-N

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Tafinlar	Capsule	50 mg/1	Oral	Novartis Pharmaceuticals Corporation	2016-04-12	Not applicable
Tafinlar	Capsule	75 mg	Oral	Novartis Europharm Limited	2021-03-17	Not applicable
Tafinlar	Capsule	50 mg/1	Oral	Glaxosmithkline Inc	2013-06-10	2018-08-31
Tafinlar	Tablet, for suspension	10 mg	Oral	Novartis	Not applicable	Not applicable
Tafinlar	Capsule	50 mg	Oral	Novartis	2013-08-28	Not applicable
Tafinlar	Capsule	50 mg/1	Oral	Glaxosmithkline Inc	2013-06-10	Not applicable
Tafinlar	Capsule	50 mg	Oral	Novartis Europharm Limited	2021-03-17	Not applicable
Tafinlar	Capsule	75 mg/1	Oral	Glaxosmithkline Inc	2013-06-10	Not applicable
Tafinlar	Tablet, for suspension	10 mg/1	Oral	Novartis Pharmaceuticals Corporation	2023-03-16	Not applicable
Tafinlar	Capsule	75 mg/1	Oral	Novartis Pharmaceuticals Corporation	2016-04-01	Not applicable

Categories

ATC Codes

L01EC02 — Dabrafenib

• L01EC — B-Raf serine-threonine kinase (BRAF) inhibitors
• L01E — PROTEIN KINASE INHIBITORS
• L01 — ANTINEOPLASTIC AGENTS
• L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Categories

• Amines
• Antineoplastic Agents
• Antineoplastic and Immunomodulating Agents
• B-Raf serine-threonine kinase (BRAF) inhibitors
• BCRP/ABCG2 Inhibitors
• BCRP/ABCG2 Substrates
• Cytochrome P-450 CYP1A2 Inhibitors
• Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
• Cytochrome P-450 CYP2B6 Inducers
• Cytochrome P-450 CYP2B6 Inducers (strength unknown)
• Cytochrome P-450 CYP2B6 Inhibitors
• Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)
• Cytochrome P-450 CYP2C19 Inducers
• Cytochrome P-450 CYP2C19 Inducers (strength unknown)
• Cytochrome P-450 CYP2C19 Inhibitors
• Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
• Cytochrome P-450 CYP2C19 Substrates
• Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index
• Cytochrome P-450 CYP2C8 Inducers
• Cytochrome P-450 CYP2C8 Inducers (strength unknown)
• Cytochrome P-450 CYP2C8 Inducers (weak)
• Cytochrome P-450 CYP2C8 Inhibitors
• Cytochrome P-450 CYP2C8 Inhibitors (strong)
• Cytochrome P-450 CYP2C8 Substrates
• Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index
• Cytochrome P-450 CYP2C9 Inducers
• Cytochrome P-450 CYP2C9 Inducers (strength unknown)
• Cytochrome P-450 CYP2C9 Inducers (strong)
• Cytochrome P-450 CYP2C9 Inhibitors
• Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
• Cytochrome P-450 CYP2C9 Substrates
• Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index
• Cytochrome P-450 CYP3A Inducers
• Cytochrome P-450 CYP3A Inhibitors
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Inducers
• Cytochrome P-450 CYP3A4 Inducers (strength unknown)
• Cytochrome P-450 CYP3A4 Inhibitors
• Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
• Cytochrome P-450 Enzyme Inducers
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Substrates
• Drugs causing inadvertant photosensitivity
• Enzyme Inhibitors
• Hydroxylamines
• Hyperglycemia-Associated Agents
• Kinase Inhibitor
• Narrow Therapeutic Index Drugs
• OAT1/SLC22A6 inhibitors
• OAT3/SLC22A8 Inhibitors
• OATP1B1/SLCO1B1 Inhibitors
• OATP1B1/SLCO1B1 Substrates
• OATP1B3 inhibitors
• OATP1B3 substrates
• OCT2 Inhibitors
• Organic Anion Transporter 1 Inhibitors
• Organic Anion Transporting Polypeptide 1B1 Inhibitors
• Organic Anion Transporting Polypeptide 1B3 Inhibitors
• P-glycoprotein substrates
• P-glycoprotein substrates with a Narrow Therapeutic Index
• Photosensitizing Agents
• Potential QTc-Prolonging Agents
• Protein Kinase Inhibitors
• Proto-Oncogene Proteins B-raf, antagonists & inhibitors
• QTc Prolonging Agents
• UGT1A1 Inhibitors

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as sulfanilides. These are organic aromatic compounds containing a sulfanilide moiety, with the general structure RS(=O)(=O)NC1=CC=CC=C1.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Sulfanilides

Direct Parent

Sulfanilides

Alternative Parents

Benzenesulfonamides / Benzenesulfonyl compounds / 2,4,5-trisubstituted thiazoles / Fluorobenzenes / Aminopyrimidines and derivatives / Organosulfonamides / Aryl fluorides / Heteroaromatic compounds / Aminosulfonyl compounds / Azacyclic compounds / Primary amines / Organopnictogen compounds / Organofluorides / Organic oxides / Hydrocarbon derivatives

show 5 more

Substituents

2,4,5-trisubstituted 1,3-thiazole / Amine / Aminopyrimidine / Aminosulfonyl compound / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Azole / Benzenesulfonamide / Benzenesulfonyl group / Fluorobenzene / Halobenzene / Heteroaromatic compound / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organic sulfonic acid or derivatives / Organofluoride / Organohalogen compound / Organoheterocyclic compound / Organonitrogen compound / Organopnictogen compound / Organosulfonic acid amide / Organosulfonic acid or derivatives / Organosulfur compound / Primary amine / Pyrimidine / Sulfanilide / Sulfonyl / Thiazole

show 22 more

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

organofluorine compound, aminopyrimidine, sulfonamide, 1,3-thiazole (CHEBI:75045)

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

QGP4HA4G1B

CAS number

1195765-45-7

InChI Key

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

References

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. [Article]
2. 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. [Article]
3. Suo Z, Xiong X, Sun Q, Zhao L, Tang P, Hou Q, Zhang Y, Wu D, Li H: Investigation on the Interaction of Dabrafenib with Human Serum Albumin Using Combined Experiment and Molecular Dynamics Simulation: Exploring the Binding Mechanism, Esterase-like Activity, and Antioxidant Activity. Mol Pharm. 2018 Dec 3;15(12):5637-5645. doi: 10.1021/acs.molpharmaceut.8b00806. Epub 2018 Nov 20. [Article]
4. Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, Lichinitser M, Dummer R, Grange F, Mortier L, Chiarion-Sileni V, Drucis K, Krajsova I, Hauschild A, Lorigan P, Wolter P, Long GV, Flaherty K, Nathan P, Ribas A, Martin AM, Sun P, Crist W, Legos J, Rubin SD, Little SM, Schadendorf D: Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015 Jan 1;372(1):30-9. doi: 10.1056/NEJMoa1412690. Epub 2014 Nov 16. [Article]
5. Millet A, Martin AR, Ronco C, Rocchi S, Benhida R: Metastatic Melanoma: Insights Into the Evolution of the Treatments and Future Challenges. Med Res Rev. 2017 Jan;37(1):98-148. doi: 10.1002/med.21404. Epub 2016 Aug 29. [Article]
6. Ascierto PA, Kirkwood JM, Grob JJ, Simeone E, Grimaldi AM, Maio M, Palmieri G, Testori A, Marincola FM, Mozzillo N: The role of BRAF V600 mutation in melanoma. J Transl Med. 2012 Jul 9;10:85. doi: 10.1186/1479-5876-10-85. [Article]
7. Sullivan RJ, Flaherty KT: BRAF in Melanoma: Pathogenesis, Diagnosis, Inhibition, and Resistance. J Skin Cancer. 2011;2011:423239. doi: 10.1155/2011/423239. Epub 2011 Nov 17. [Article]
8. McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, Chang F, Lehmann B, Terrian DM, Milella M, Tafuri A, Stivala F, Libra M, Basecke J, Evangelisti C, Martelli AM, Franklin RA: Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta. 2007 Aug;1773(8):1263-84. doi: 10.1016/j.bbamcr.2006.10.001. Epub 2006 Oct 7. [Article]
9. Allan LA, Morrice N, Brady S, Magee G, Pathak S, Clarke PR: Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK. Nat Cell Biol. 2003 Jul;5(7):647-54. [Article]
10. Holderfield M, Deuker MM, McCormick F, McMahon M: Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond. Nat Rev Cancer. 2014 Jul;14(7):455-67. doi: 10.1038/nrc3760. [Article]
11. Brugnara S, Sicher M, Bonandini EM, Donner D, Chierichetti F, Barbareschi M, Girardelli CR, Caffo O: Treatment with combined dabrafenib and trametinib in BRAF(V600E)-mutated metastatic malignant melanoma: a case of long-term complete response after treatment cessation. Drugs Context. 2018 Feb 15;7:212515. doi: 10.7573/dic.212515. eCollection 2018. [Article]
12. Ellens H, Johnson M, Lawrence SK, Watson C, Chen L, Richards-Peterson LE: Prediction of the Transporter-Mediated Drug-Drug Interaction Potential of Dabrafenib and Its Major Circulating Metabolites. Drug Metab Dispos. 2017 Jun;45(6):646-656. doi: 10.1124/dmd.116.073932. Epub 2017 Mar 20. [Article]
13. Dabrafenib [Link]
14. Drug Duo, Tafinlar and Mekinist, Approved for Aggressive Thyroid Cancer [Link]
15. FDA grants regular approval to dabrafenib and trametinib combination for metastatic NSCLC with BRAF V600E mutation [Link]
16. Novartis receives FDA approval of Tafinlar® + Mekinist® for adjuvant treatment of BRAF V600-mutant melanoma [Link]
17. Dabrafenib [Link]
18. Cancer. gov Dabrafenib [Link]
19. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600–Mutant Anaplastic Thyroid Cancer [Link]
20. FDA Approved Drug Proucts: TAFINLAR® (dabrafenib) capsules, for oral use [Link]
21. Santa Cruz Biotech: Dabrafenib MSDS [Link]
22. GSK: Dabrafenib MSDS [Link]
23. FDA Approved Drug Products: TAFINLAR (dabrafenib) Oral Capsules or Tablets for Oral Suspension (March 2023) [Link]
24. FDA Approved Drug Products: TAFINLAR (dabrafenib) Oral Capsules or Tablets for Oral Suspension (June 2023) [Link]
25. NZ DrugSafe Tafinlar [File]
26. Monograph, Tafinlar [File]

External Links

Human Metabolome Database

HMDB0250818

KEGG Drug

D10064

PubChem Compound

44462760

PubChem Substance

175427150

ChemSpider

25948204

BindingDB

50428286

RxNav

1424911

ChEBI

75045

ChEMBL

CHEMBL2028663

ZINC

ZINC000068153186

PDBe Ligand

P06

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Dabrafenib

PDB Entries

4xv2 / 5csw / 5hie / 6hj2 / 6v2u / 7riv

FDA label

Download (418 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Recruiting	Treatment	Anaplastic Astrocytoma (AA) / Anaplastic Ganglioglioma / Anaplastic Oligodendroglioma (AO) / Angiocentric glioma / Astrocytoma / Central Neurocytoma / Cerebellar Liponeurocytoma / Chordoid Glioma of Third Ventricle / Desmoplastic Infantile Astrocytoma and Ganglioglioma / Diffuse Astrocytoma / Dysplastic Gangliocytoma of Cerebrellum / Extraventricular Neurocytoma / Gangliocytoma / Ganglioglioma / Giant Cell Astrocytoma / High Grade Glioma: Glioblastoma (GBM) / Neurofibromatosis, type 1 (von Recklinghausen's disease) / Oligodendroglioma, Childhood / Papillary Glioneuronal Tumor / Pilocytic Astrocytoma / Pleomorphic Xanthoastrocytoma / Pleomorphic Xanthoastrocytoma, Anaplastic / Rosette-forming Glioneurona Tumor	1
4	Recruiting	Treatment	High Grade Glioma (HGG) / Melanoma / Non-Small Cell Lung Cancer (NSCLC) / Rare Cancers / Solid Tumors	1
3	Active Not Recruiting	Treatment	Clinical Stage III Cutaneous Melanoma AJCC v8 / Clinical Stage IV Cutaneous Melanoma AJCC v8 / Metastatic Melanoma / Recurrent Melanoma / Unresectable Melanoma	1
3	Active Not Recruiting	Treatment	Melanoma	1
3	Completed	Treatment	Cancer	1
3	Completed	Treatment	Malignant Melanoma	1
3	Completed	Treatment	Melanoma	3
3	Recruiting	Health Services Research	Soft Tissue Sarcoma	1
3	Recruiting	Treatment	Differentiated Thyroid Cancer (DTC)	1
2	Active Not Recruiting	Screening	Advanced Malignant Solid Tumor / Bladder Carcinoma / Breast Carcinoma / Carcinoma of the Head and Neck / Carcinoma of the Skin / Cervical Carcinoma / Colon Carcinoma / Colorectal Carcinoma (CRC) / Endometrial Carcinoma / Esophageal Carcinoma / Gastric Carcinoma / Glioma / Liver and Intrahepatic Bile Duct Carcinoma / Lung Carcinoma / Lymphoma / Malignant Uterine Neoplasm / Melanoma / Multiple Myeloma (MM) / Ovarian Carcinoma / Pancreatic Carcinoma / Prostate Carcinoma / Rectal Carcinoma / Recurrent Bladder Carcinoma / Recurrent Breast Carcinoma / Recurrent Cervical Carcinoma / Recurrent Colon Carcinoma / Recurrent Colorectal Carcinoma / Recurrent Esophageal Carcinoma / Recurrent Gastric Carcinoma / Recurrent Gliomas / Recurrent Head and Neck Carcinoma / Recurrent Liver Carcinoma / Recurrent Lung Carcinoma / Recurrent Lymphoma / Recurrent Malignant Solid Neoplasm / Recurrent Melanoma / Recurrent multiple myeloma / Recurrent Ovarian Carcinoma / Recurrent Pancreatic Carcinoma / Recurrent Prostate Carcinoma / Recurrent Rectal Carcinoma / Recurrent Skin Carcinoma / Recurrent Thyroid Gland Carcinoma / Recurrent Uterine Corpus Cancer / Refractory Lymphomas / Refractory Malignant Solid Neoplasm / Refractory Multiple Myeloma / Renal Carcinoma / Thyroid Gland Carcinoma / Uterine Corpus Cancer	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Capsule	Oral	50 mg/1
Capsule	Oral	75 mg/1
Tablet, for suspension	Oral	10 mg
Tablet, for suspension	Oral	10 mg/1
Capsule	Oral	50 mg
Capsule	Oral	75 mg
Capsule, coated	Oral	50 mg
Capsule, coated	Oral	75 mg

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US7994185	Yes	2011-08-09	2030-07-20
US8415345	Yes	2013-04-09	2030-07-20
US9233956	Yes	2016-01-12	2029-11-04
US8703781	Yes	2014-04-22	2031-04-15
US8835443	Yes	2014-09-16	2025-12-10
US8952018	Yes	2015-02-10	2031-04-15
US10869869	Yes	2020-12-22	2034-03-02
US11504333	No	2018-06-29	2038-06-29

Properties

State

Solid

Experimental Properties

Property	Value	Source
boiling point (°C)	653.7	https://datasheets.scbt.com/sds/aghs/en/sc-364477.pdf
water solubility	very slightly soluble at pH 1	http://www.medsafe.govt.nz/profs/Datasheet/t/tafinlarcap.pdf
logP	2.9	http://www.medsafe.govt.nz/profs/Datasheet/t/tafinlarcap.pdf
pKa	-1.5	http://www.medsafe.govt.nz/profs/Datasheet/t/tafinlarcap.pdf

Predicted Properties

Property	Value	Source
Water Solubility	0.00327 mg/mL	ALOGPS
logP	5.44	ALOGPS
logP	5.46	Chemaxon
logS	-5.2	ALOGPS
pKa (Strongest Acidic)	7.16	Chemaxon
pKa (Strongest Basic)	2.97	Chemaxon
Physiological Charge	-1	Chemaxon
Hydrogen Acceptor Count	6	Chemaxon
Hydrogen Donor Count	2	Chemaxon
Polar Surface Area	110.86 Å2	Chemaxon
Rotatable Bond Count	5	Chemaxon
Refractivity	127.51 m3·mol-1	Chemaxon
Polarizability	49.71 Å3	Chemaxon
Number of Rings	4	Chemaxon
Bioavailability	0	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9944
Blood Brain Barrier	+	0.7232
Caco-2 permeable	+	0.5069
P-glycoprotein substrate	Non-substrate	0.7965
P-glycoprotein inhibitor I	Non-inhibitor	0.6468
P-glycoprotein inhibitor II	Non-inhibitor	0.7039
Renal organic cation transporter	Non-inhibitor	0.8694
CYP450 2C9 substrate	Non-substrate	0.8233
CYP450 2D6 substrate	Non-substrate	0.7346
CYP450 3A4 substrate	Non-substrate	0.5834
CYP450 1A2 substrate	Inhibitor	0.5219
CYP450 2C9 inhibitor	Inhibitor	0.5
CYP450 2D6 inhibitor	Non-inhibitor	0.8459
CYP450 2C19 inhibitor	Non-inhibitor	0.5
CYP450 3A4 inhibitor	Inhibitor	0.7531
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.8612
Ames test	Non AMES toxic	0.7078
Carcinogenicity	Non-carcinogens	0.8093
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	2.4329 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9848
hERG inhibition (predictor II)	Non-inhibitor	0.7704

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Targets

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Details1. Serine/threonine-protein kinase B-raf

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Inhibitor

Curator comments

Although dabrafenib can target the wild-type BRAF, it is mostly used to inhibit mutated forms of BRAF, such as BRAF V600E, BRAF V600K, and BRAF V600D.[L41955]

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, a...

Gene Name

BRAF

Uniprot ID

P15056

Uniprot Name

Serine/threonine-protein kinase B-raf

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. [Article]
2. FDA Approved Drug Proucts: TAFINLAR® (dabrafenib) capsules, for oral use [Link]

Details2. RAF proto-oncogene serine/threonine-protein kinase

Kind

Protein

Organism

Humans

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 determin...

Gene Name

RAF1

Uniprot ID

P04049

Uniprot Name

RAF proto-oncogene serine/threonine-protein kinase

Molecular Weight

73051.025 Da

References

1. FDA Approved Drug Proucts: TAFINLAR® (dabrafenib) capsules, for oral use [Link]
2. Monograph, Tafinlar [File]

Details3. Serine/threonine-protein kinase SIK1

Kind

Protein

Organism

Humans

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. Pho...

Gene Name

SIK1

Uniprot ID

P57059

Uniprot Name

Serine/threonine-protein kinase SIK1

Molecular Weight

84901.25 Da

References

1. FDA Approved Drug Proucts: TAFINLAR® (dabrafenib) capsules, for oral use [Link]
2. Monograph, Tafinlar [File]

Details4. Serine/threonine-protein kinase Nek11

Kind

Protein

Organism

Humans

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 requir...

Gene Name

NEK11

Uniprot ID

Q8NG66

Uniprot Name

Serine/threonine-protein kinase Nek11

Molecular Weight

74191.62 Da

References

1. FDA Approved Drug Proucts: TAFINLAR® (dabrafenib) capsules, for oral use [Link]
2. Monograph, Tafinlar [File]

Details5. LIM domain kinase 1

Kind

Protein

Organism

Humans

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 up...

Gene Name

LIMK1

Uniprot ID

P53667

Uniprot Name

LIM domain kinase 1

Molecular Weight

72584.4 Da

References

1. FDA Approved Drug Proucts: TAFINLAR® (dabrafenib) capsules, for oral use [Link]
2. Monograph, Tafinlar [File]

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Drug created at June 24, 2013 21:54 / Updated at September 28, 2023 01:14