dabrafenib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
Raf (Rapidely Accelerated Fibrosarcoma) kinase inhibitors 4801 1195765-45-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • GSK2118436B
  • dabrafenib mesylate
  • tafinlar
  • dabrafenib
  • GSK2118436
  • dabrafenib mesilate
Dabrafenib 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. Dabrafenib inhibits cell growth of various BRAF V600 mutation-positive tumors in vitro and in vivo.
  • Molecular weight: 519.56
  • Formula: C23H20F3N5O2S2
  • CLOGP: 4.61
  • LIPINSKI: 1
  • HAC: 7
  • HDO: 2
  • TPSA: 110.86
  • ALOGS: -5.20
  • ROTB: 5

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ
Vd (Volume of distribution) 0.65 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 2.86 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.00 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 2.60 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Aug. 26, 2013 EMA Novartis Europharm Limited
May 29, 2013 FDA NOVARTIS PHARMS CORP

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Pyrexia 1194.90 21.03 814 9693 347988 46327567
Malignant neoplasm progression 564.82 21.03 280 10227 64646 46610909
Chills 306.98 21.03 217 10290 95815 46579740
Metastatic malignant melanoma 268.50 21.03 62 10445 1282 46674273
Uveitis 179.42 21.03 69 10438 8572 46666983
Malignant melanoma 171.52 21.03 70 10437 10164 46665391
Metastases to central nervous system 161.97 21.03 69 10438 11152 46664403
Death 143.65 21.03 264 10243 335284 46340271
Panniculitis 130.85 21.03 49 10458 5655 46669900
Malignant melanoma stage IV 104.37 21.03 17 10490 43 46675512
Ejection fraction decreased 103.42 21.03 59 10448 17878 46657677
Rash 84.11 21.03 221 10286 356291 46319264
Visual impairment 62.47 21.03 76 10431 66613 46608942
Dermatitis acneiform 58.61 21.03 25 10482 4045 46671510
Blood creatine phosphokinase increased 58.31 21.03 49 10458 27675 46647880
Drug ineffective 54.41 21.03 44 10463 677794 45997761
Erythema nodosum 50.40 21.03 22 10485 3764 46671791
Anaplastic thyroid cancer 46.13 21.03 8 10499 33 46675522
Chorioretinopathy 43.80 21.03 13 10494 728 46674827
Metastases to meninges 38.60 21.03 15 10492 1912 46673643
Vogt-Koyanagi-Harada disease 36.68 21.03 8 10499 126 46675429
Hyperpyrexia 36.58 21.03 16 10491 2750 46672805
Drug hypersensitivity 35.71 21.03 6 10501 243819 46431736
Metastasis 35.55 21.03 18 10489 4294 46671261
Iridocyclitis 34.58 21.03 14 10493 1986 46673569
Cutaneous sarcoidosis 33.81 21.03 9 10498 338 46675217
Serous retinal detachment 31.16 21.03 7 10500 127 46675428
Product use in unapproved indication 31.00 21.03 65 10442 90208 46585347
Hyperkeratosis 30.22 21.03 17 10490 5008 46670547
Rash maculo-papular 29.77 21.03 34 10473 27840 46647715
Vision blurred 29.26 21.03 59 10448 79649 46595906
Systemic inflammatory response syndrome 29.16 21.03 17 10490 5354 46670201
Erythema multiforme 28.73 21.03 21 10486 9683 46665872
Second primary malignancy 28.44 21.03 18 10489 6566 46668989
Squamous cell carcinoma 27.94 21.03 19 10488 7817 46667738
Vomiting 27.56 21.03 185 10322 452609 46222946
Metastases to lung 26.91 21.03 21 10486 10675 46664880
Skin toxicity 26.52 21.03 14 10493 3640 46671915
Retinal detachment 24.71 21.03 15 10492 5085 46670470
Myalgia 24.57 21.03 72 10435 123016 46552539
Pneumonitis 24.35 21.03 31 10476 28389 46647166
Dehydration 24.27 21.03 85 10422 159455 46516100
Blood lactate dehydrogenase increased 23.59 21.03 26 10481 20474 46655081
Off label use 23.18 21.03 31 10476 379810 46295745
Fall 23.14 21.03 24 10483 329073 46346482
Acute polyneuropathy 22.94 21.03 6 10501 210 46675345
Melanoma recurrent 22.79 21.03 5 10502 81 46675474
Nausea 22.26 21.03 244 10263 687210 45988345
Hepatocellular injury 21.89 21.03 30 10477 29492 46646063
Aspartate aminotransferase increased 21.77 21.03 52 10455 78648 46596907
Rhabdomyolysis 21.69 21.03 36 10471 41873 46633682
Astrocytoma 21.43 21.03 5 10502 108 46675447
C-reactive protein increased 21.06 21.03 43 10464 58547 46617008

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Pyrexia 1133.19 20.22 921 10855 293568 29647134
Malignant neoplasm progression 559.12 20.22 349 11427 71938 29868764
Metastatic malignant melanoma 372.73 20.22 98 11678 1972 29938730
Chills 332.76 20.22 254 11522 72084 29868618
Metastases to central nervous system 320.49 20.22 117 11659 7167 29933535
Malignant melanoma 191.50 20.22 81 11695 7330 29933372
Ejection fraction decreased 168.71 20.22 93 11683 15082 29925620
Death 155.61 20.22 394 11382 356889 29583813
Uveitis 112.66 20.22 51 11725 5426 29935276
Metastases to liver 85.05 20.22 55 11721 11910 29928792
Malignant melanoma stage IV 81.13 20.22 15 11761 48 29940654
Metastases to stomach 71.07 20.22 14 11762 68 29940634
Basal cell carcinoma 70.44 20.22 55 11721 16013 29924689
Squamous cell carcinoma 62.90 20.22 43 11733 10207 29930495
Metastases to lung 57.85 20.22 37 11739 7858 29932844
Rash 56.00 20.22 184 11592 191705 29748997
Metastases to peritoneum 53.87 20.22 21 11755 1536 29939166
Second primary malignancy 52.13 20.22 32 11744 6324 29934378
C-reactive protein increased 51.68 20.22 74 11702 43399 29897303
Visual impairment 50.42 20.22 61 11715 30377 29910325
Blood creatine phosphokinase increased 49.73 20.22 73 11703 43775 29896927
Panniculitis 46.12 20.22 16 11760 841 29939861
Blood lactate dehydrogenase increased 45.58 20.22 48 11728 20553 29920149
Metastases to skin 45.22 20.22 13 11763 367 29940335
Metastases to meninges 44.43 20.22 17 11759 1182 29939520
Serous retinal detachment 43.44 20.22 12 11764 292 29940410
Procalcitonin increased 41.96 20.22 16 11760 1102 29939600
Chorioretinopathy 41.28 20.22 17 11759 1435 29939267
Hyperkeratosis 41.24 20.22 22 11754 3335 29937367
Malignant mesenteric neoplasm 39.78 20.22 8 11768 44 29940658
Jejunal ulcer perforation 36.55 20.22 8 11768 70 29940632
Off label use 36.42 20.22 27 11749 249263 29691439
Metastasis 36.03 20.22 20 11756 3278 29937424
Metastases to bone 35.84 20.22 30 11746 9628 29931074
Disease progression 35.26 20.22 89 11687 79785 29860917
Gastrointestinal wall thickening 33.92 20.22 13 11763 908 29939794
Erythema nodosum 33.53 20.22 13 11763 937 29939765
Metastases to lymph nodes 32.55 20.22 20 11756 3957 29936745
Tissue infiltration 31.51 20.22 7 11769 66 29940636
Haemophagocytic lymphohistiocytosis 31.43 20.22 28 11748 9763 29930939
Metastases to heart 31.40 20.22 8 11768 141 29940561
Intestinal metastasis 30.78 20.22 8 11768 153 29940549
Product use in unapproved indication 30.34 20.22 80 11696 73613 29867089
Eastern Cooperative Oncology Group performance status 30.31 20.22 6 11770 30 29940672
Omental necrosis 30.31 20.22 6 11770 30 29940672
Mesenteric neoplasm 29.99 20.22 6 11770 32 29940670
Anaplastic thyroid cancer 29.84 20.22 5 11771 7 29940695
Ureteral disorder 29.77 20.22 8 11768 175 29940527
Hyperpyrexia 29.18 20.22 16 11760 2561 29938141
Brain neoplasm 28.06 20.22 16 11760 2761 29937941
Drug interaction 27.37 20.22 23 11753 199545 29741157
Fatigue 26.17 20.22 215 11561 320458 29620244
Toxicity to various agents 26.09 20.22 19 11757 177164 29763538
Drug ineffective 25.93 20.22 60 11716 340327 29600375
Body temperature fluctuation 23.53 20.22 11 11765 1258 29939444
Decreased appetite 23.00 20.22 118 11658 149792 29790910
Inflammatory bowel disease 22.60 20.22 13 11763 2280 29938422
Small intestine carcinoma 22.59 20.22 8 11768 447 29940255
Iridocyclitis 22.43 20.22 11 11765 1398 29939304
Papilloedema 22.27 20.22 13 11763 2343 29938359
Leukoderma 21.64 20.22 5 11771 57 29940645
Abdominal lymphadenopathy 21.26 20.22 8 11768 531 29940171
Tumour invasion 20.78 20.22 7 11769 336 29940366
Anxiety 20.60 20.22 5 11771 89866 29850836
BRAF V600E mutation positive 20.56 20.22 4 11772 18 29940684
Metastases to adrenals 20.31 20.22 9 11767 909 29939793

Pharmacologic Action:

SourceCodeDescription
ATC L01EC02 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
B-Raf serine-threonine kinase (BRAF) inhibitors
FDA MoA N0000175076 Protein Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA MoA N0000185506 Cytochrome P450 3A4 Inducers
FDA MoA N0000185507 Cytochrome P450 2C9 Inducers
FDA MoA N0000185607 Cytochrome P450 2C19 Inducers
FDA MoA N0000187063 Cytochrome P450 2C8 Inducers
FDA MoA N0000187064 Cytochrome P450 2B6 Inducers
FDA MoA N0000190107 Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA N0000190108 Organic Anion Transporting Polypeptide 1B3 Inhibitors
FDA MoA N0000190110 Organic Anion Transporter 1 Inhibitors
FDA MoA N0000190111 Organic Anion Transporter 3 Inhibitors
FDA MoA N0000190113 Breast Cancer Resistance Protein Inhibitors
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:75047 b-raf inhibitors
CHEBI has role CHEBI:149553 anti-coronaviral agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Metastatic malignant melanoma indication 443493003
Malignant Melanoma with BRAF V600E Mutation indication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.56 acidic
pKa2 3.35 Basic
pKa3 0.43 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 50MG BASE TAFINLAR NOVARTIS N202806 May 29, 2013 RX CAPSULE ORAL Jan. 9, 2021 DABRAFENIB IN COMBO WITH TRAMETINIB FOR TX. OF PTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST. THIS INDICATION IS BASED ON THE DEMONSTRATION OF DURABLE RESPONSE RATE
EQ 75MG BASE TAFINLAR NOVARTIS N202806 May 29, 2013 RX CAPSULE ORAL Jan. 9, 2021 DABRAFENIB IN COMBO WITH TRAMETINIB FOR TX. OF PTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST. THIS INDICATION IS BASED ON THE DEMONSTRATION OF DURABLE RESPONSE RATE
EQ 50MG BASE TAFINLAR NOVARTIS N202806 May 29, 2013 RX CAPSULE ORAL April 30, 2021 DABRAFENIB IN COMBINULLTION WITH TRAMETINIB FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 75MG BASE TAFINLAR NOVARTIS N202806 May 29, 2013 RX CAPSULE ORAL April 30, 2021 DABRAFENIB IN COMBINULLTION WITH TRAMETINIB FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 50MG BASE TAFINLAR NOVARTIS N202806 May 29, 2013 RX CAPSULE ORAL May 4, 2021 DABRAFENIB IN COMBINULLTION WITH TRAMETINIB FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANULLPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONULLL TREATMENT OPTIONS
EQ 75MG BASE TAFINLAR NOVARTIS N202806 May 29, 2013 RX CAPSULE ORAL May 4, 2021 DABRAFENIB IN COMBINULLTION WITH TRAMETINIB FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANULLPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONULLL TREATMENT OPTIONS
EQ 50MG BASE TAFINLAR NOVARTIS N202806 May 29, 2013 RX CAPSULE ORAL Oct. 6, 2022 ADDITION OF STUDY BRF117277, A NON-RANDOMIZED, OPEN-LABEL, MULTI-CENTER, MULTI-COHORT TRIAL OF DABRAFENIB PLUS TRAMETINIB IN SUBJECTS WITH BRAF MUTATION-POSITIVE MELANOMA THAT HAS METASTASIZED TO THE BRAIN
EQ 75MG BASE TAFINLAR NOVARTIS N202806 May 29, 2013 RX CAPSULE ORAL Oct. 6, 2022 ADDITION OF STUDY BRF117277, A NON-RANDOMIZED, OPEN-LABEL, MULTI-CENTER, MULTI-COHORT TRIAL OF DABRAFENIB PLUS TRAMETINIB IN SUBJECTS WITH BRAF MUTATION-POSITIVE MELANOMA THAT HAS METASTASIZED TO THE BRAIN
EQ 50MG BASE TAFINLAR NOVARTIS N202806 May 29, 2013 RX CAPSULE ORAL June 22, 2024 DABRAFENIB IN COMBINULLTION WITH TRAMETINIB, FOR THE TX. OF PTS WITH METASTATIC NON-SMALL CELL LUNG CANCER WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST
EQ 75MG BASE TAFINLAR NOVARTIS N202806 May 29, 2013 RX CAPSULE ORAL June 22, 2024 DABRAFENIB IN COMBINULLTION WITH TRAMETINIB, FOR THE TX. OF PTS WITH METASTATIC NON-SMALL CELL LUNG CANCER WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST
EQ 50MG BASE TAFINLAR NOVARTIS N202806 May 29, 2013 RX CAPSULE ORAL April 30, 2025 TRAMETINIB IS INDICATED, IN COMBINULLTION WITH DABRAFENIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 75MG BASE TAFINLAR NOVARTIS N202806 May 29, 2013 RX CAPSULE ORAL April 30, 2025 TRAMETINIB IS INDICATED, IN COMBINULLTION WITH DABRAFENIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 50MG BASE TAFINLAR NOVARTIS N202806 May 29, 2013 RX CAPSULE ORAL May 4, 2025 TRAMETINIB AND DABRAFENIB IN COMBINULLTION, FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANULLPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONULLL TREATMENT OPTIONS
EQ 75MG BASE TAFINLAR NOVARTIS N202806 May 29, 2013 RX CAPSULE ORAL May 4, 2025 TRAMETINIB AND DABRAFENIB IN COMBINULLTION, FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANULLPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONULLL TREATMENT OPTIONS

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Serine/threonine-protein kinase B-raf Kinase INHIBITOR IC50 9.15 WOMBAT-PK CHEMBL
TGF-beta receptor type-1 Kinase IC50 5.43 CHEMBL
RAF proto-oncogene serine/threonine-protein kinase Kinase IC50 6.82 CHEMBL
Serine/threonine-protein kinase A-Raf Kinase IC50 7.59 CHEMBL

External reference:

IDSource
D10064 KEGG_DRUG
1195768-06-9 SECONDARY_CAS_RN
4032496 VANDF
C3467876 UMLSCUI
CHEBI:75045 CHEBI
P06 PDB_CHEM_ID
CHEMBL2028663 ChEMBL_ID
CHEMBL2105729 ChEMBL_ID
DB08912 DRUGBANK_ID
C561627 MESH_SUPPLEMENTAL_RECORD_UI
44462760 PUBCHEM_CID
6494 IUPHAR_LIGAND_ID
9458 INN_ID
QGP4HA4G1B UNII
1424911 RXNORM
203107 MMSL
29476 MMSL
29650 MMSL
d08103 MMSL
015042 NDDF
015043 NDDF
703641001 SNOMEDCT_US
703642008 SNOMEDCT_US
703646006 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Tafinlar HUMAN PRESCRIPTION DRUG LABEL 1 0078-0681 CAPSULE 75 mg ORAL NDA 32 sections
Tafinlar HUMAN PRESCRIPTION DRUG LABEL 1 0078-0682 CAPSULE 50 mg ORAL NDA 32 sections