encorafenib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
Raf (Rapidely Accelerated Fibrosarcoma) kinase inhibitors 5289 1269440-17-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • encorafenib
  • braftovi
  • NVP-LGX818-NXA
Encorafenib is a kinase inhibitor that targets BRAF V600E, as well as wild-type BRAF and CRAF. Mutations in the BRAF gene, such as BRAF V600E, can result in constitutively activated BRAF kinases that may stimulate tumor cell growth. Encorafenib was also able to bind to other kinases in vitro including JNK1, JNK2, JNK3, LIMK1, LIMK2, MEK4, and STK36 and substantially reduce ligand binding to these kinases at clinically achievable concentrations. Encorafenib inhibited in vitro growth of tumor cell lines expressing BRAF V600 E, D, and K mutations. In mice implanted with tumor cells expressing BRAF V600E, encorafenib induced tumor regressions associated with RAF/MEK/ERK pathway suppression.
  • Molecular weight: 540.01
  • Formula: C22H27ClFN7O4S
  • CLOGP: 2.88
  • LIPINSKI: 2
  • HAC: 11
  • HDO: 3
  • TPSA: 140.13
  • ALOGS: -4.68
  • ROTB: 9

  • Status: ONP

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

Drug dosage:

DoseUnitRoute
0.45 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ

Approvals:

DateAgencyCompanyOrphan
June 27, 2018 FDA ARRAY BIOPHARMA INC
Jan. 8, 2019 PMDA Ono Pharmaceutical Co., Ltd.

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
Serous retinal detachment 550.53 30.64 75 3060 292 63485595
Neoplasm progression 181.51 30.64 68 3067 36360 63449527
Serous retinopathy 118.33 30.64 15 3120 27 63485860
Death 93.57 30.64 103 3032 374278 63111609
Retinal detachment 77.59 30.64 23 3112 5946 63479941
Second primary malignancy 75.19 30.64 24 3111 7929 63477958
Off label use 69.66 30.64 121 3014 674341 62811546
Pyrexia 64.30 30.64 96 3039 470382 63015505
Colitis 64.12 30.64 36 3099 48492 63437395
Macular detachment 58.24 30.64 9 3126 95 63485792
Hepatic function abnormal 47.55 30.64 27 3108 37115 63448772
Uveitis 43.30 30.64 18 3117 12535 63473352
Hospice care 40.11 30.64 15 3120 7917 63477970
Diarrhoea 40.07 30.64 100 3035 715266 62770621
Dermatitis acneiform 38.81 30.64 13 3122 4983 63480904
Disease progression 37.98 30.64 38 3097 122720 63363167
Decreased appetite 36.66 30.64 53 3082 250999 63234888
Nausea 34.50 30.64 106 3029 854365 62631522
Intestinal obstruction 33.05 30.64 20 3115 30879 63455008
Large intestinal ulcer 30.93 30.64 10 3125 3434 63482453

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
Serous retinal detachment 499.11 27.21 80 3244 532 34953075
Neoplasm progression 265.57 27.21 95 3229 23205 34930402
Serous retinopathy 122.48 27.21 19 3305 98 34953509
Second primary malignancy 63.51 27.21 25 3299 7861 34945746
Death 53.85 27.21 117 3207 397932 34555675
Nausea 44.82 27.21 99 3225 339809 34613798
Disease progression 44.49 27.21 53 3271 108024 34845583
Blood creatine phosphokinase increased 43.08 27.21 35 3289 44822 34908785
Dermatitis acneiform 40.81 27.21 17 3307 6172 34947435
Vision blurred 36.19 27.21 32 3292 45931 34907676
Pyrexia 34.10 27.21 88 3236 332925 34620682
Off label use 32.35 27.21 100 3224 419424 34534183
Subretinal fluid 29.38 27.21 7 3317 403 34953204

FDA Adverse Event Reporting System (Geriatric)

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
Serous retinal detachment 1017.06 26.31 155 6142 879 79737212
Neoplasm progression 407.34 26.31 153 6144 51529 79686562
Serous retinopathy 234.41 26.31 34 6263 127 79737964
Death 149.25 26.31 202 6095 566312 79171779
Second primary malignancy 125.66 26.31 46 6251 14304 79723787
Off label use 92.35 26.31 213 6084 907002 78831089
Retinal detachment 82.27 26.31 30 6267 9217 79728874
Pyrexia 80.93 26.31 170 6127 678539 79059552
Dermatitis acneiform 80.00 26.31 30 6267 9963 79728128
Blood creatine phosphokinase increased 68.37 26.31 50 6247 66040 79672051
Uveitis 68.04 26.31 31 6266 16799 79721292
Macular detachment 66.11 26.31 12 6285 215 79737876
Colitis 63.75 26.31 50 6247 73257 79664834
Vision blurred 62.89 26.31 58 6239 105840 79632251
Nausea 62.72 26.31 191 6106 957005 78781086
Hepatic function abnormal 57.47 26.31 47 6250 73060 79665031
Disease progression 56.31 26.31 71 6226 184291 79553800
Diarrhoea 55.09 26.31 173 6124 880316 78857775
Hospice care 51.35 26.31 22 6275 10302 79727789
Decreased appetite 49.27 26.31 93 6204 342325 79395766
Retinopathy 43.65 26.31 15 6282 3876 79734215
Liver disorder 36.03 26.31 36 6261 72381 79665710
Subretinal fluid 35.35 26.31 9 6288 823 79737268
Amylase increased 34.15 26.31 17 6280 11192 79726899
Large intestinal ulcer 33.36 26.31 13 6284 4784 79733307
Lipase increased 33.28 26.31 19 6278 16447 79721644
Demyelinating polyneuropathy 33.10 26.31 10 6287 1716 79736375
Macular oedema 31.69 26.31 13 6284 5461 79732630
Hepatic cytolysis 31.40 26.31 22 6275 27129 79710962
Detachment of retinal pigment epithelium 30.64 26.31 8 6289 808 79737283
Underdose 29.63 26.31 23 6274 33128 79704963
Retinal oedema 29.31 26.31 8 6289 957 79737134
Paronychia 27.26 26.31 13 6284 7795 79730296

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EC03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
B-Raf serine-threonine kinase (BRAF) inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Metastatic malignant melanoma indication 443493003
Unresectable malignant melanoma with BRAF gene mutation indication 830150003
BRAF mutation-positive colorectal cancer indication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.37 acidic
pKa2 13.42 acidic
pKa3 3.69 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
50MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 DISCN CAPSULE ORAL 8541575 Feb. 26, 2030 TREATMENT OF MELANOMA
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 8541575 Feb. 26, 2030 BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH BINIMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH A BRAF V600E OR V600K MUTATION, AS DETECTED BY AN FDA- APPROVED TEST
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 8541575 Feb. 26, 2030 BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC COLORECTAL CANCER (CRC) WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 8541575 Feb. 26, 2030 TREATMENT OF MELANOMA
50MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 DISCN CAPSULE ORAL 10005761 Aug. 27, 2030 TREATMENT OF MELANOMA
50MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 DISCN CAPSULE ORAL 9850229 Aug. 27, 2030 INDICATED IN COMBINATION WITH BINIMETINIB FOR THE TREATMENT OF MELANOMA WITH A BRAF MUTATION
50MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 DISCN CAPSULE ORAL 9850230 Aug. 27, 2030 TREATMENT OF MELANOMA WITH A BRAF MUTATION
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 10005761 Aug. 27, 2030 BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH BINIMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH A BRAF V600E OR V600K MUTATION, AS DETECTED BY AN FDA- APPROVED TEST
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 10005761 Aug. 27, 2030 BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC COLORECTAL CANCER (CRC) WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 10005761 Aug. 27, 2030 TREATMENT OF MELANOMA
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 9850229 Aug. 27, 2030 INDICATED IN COMBINATION WITH BINIMETINIB FOR THE TREATMENT OF MELANOMA WITH A BRAF MUTATION
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 9850230 Aug. 27, 2030 BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH BINIMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH A BRAF V600E OR V600K MUTATION, AS DETECTED BY AN FDA- APPROVED TEST
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 9850230 Aug. 27, 2030 BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC COLORECTAL CANCER (CRC) WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 9850230 Aug. 27, 2030 TREATMENT OF MELANOMA WITH A BRAF MUTATION
50MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 DISCN CAPSULE ORAL 9314464 July 4, 2031 TREATMENT OF MELANOMA MEDIATED BY A B-RAF PROTEIN KINASE
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 9314464 July 4, 2031 BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH BINIMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH A BRAF V600E OR V600K MUTATION, AS DETECTED BY AN FDA- APPROVED TEST
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 9314464 July 4, 2031 BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC COLORECTAL CANCER (CRC) WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 9314464 July 4, 2031 TREATMENT OF MELANOMA MEDIATED BY A B-RAF PROTEIN KINASE
50MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 DISCN CAPSULE ORAL 9763941 Nov. 21, 2032 TREATMENT OF MELANOMA
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 10258622 Nov. 21, 2032 BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC COLORECTAL CANCER (CRC) WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 9763941 Nov. 21, 2032 TREATMENT OF MELANOMA
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL 9474754 Aug. 5, 2033 BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC COLORECTAL CANCER (CRC) WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
50MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 DISCN CAPSULE ORAL April 8, 2023 ENCORAFENIB, IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULTPATIENTS WITH METASTATIC COLORECTAL CANCER WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL April 8, 2023 ENCORAFENIB, IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULTPATIENTS WITH METASTATIC COLORECTAL CANCER WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY
50MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 DISCN CAPSULE ORAL June 27, 2023 NEW CHEMICAL ENTITY
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL June 27, 2023 NEW CHEMICAL ENTITY
50MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 DISCN CAPSULE ORAL June 27, 2025 ENCORAFENIB IS INDICATED IN COMBINATION WITH BINIMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH A BRAF V600E OR V600K MUTATION, AS DETECTED BY AN FDA-APPROVED TEST
75MG BRAFTOVI ARRAY BIOPHARMA INC N210496 June 27, 2018 RX CAPSULE ORAL June 27, 2025 ENCORAFENIB IS INDICATED IN COMBINATION WITH BINIMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH A BRAF V600E OR V600K MUTATION, AS DETECTED BY AN FDA-APPROVED TEST

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
RAF proto-oncogene serine/threonine-protein kinase Kinase INHIBITOR IC50 9.52 DRUG LABEL DRUG LABEL
Serine/threonine-protein kinase B-raf Kinase INHIBITOR IC50 9.33 DRUG LABEL DRUG LABEL
Mitogen-activated protein kinase 14 Kinase IC50 5.66 CHEMBL
Mitogen-activated protein kinase kinase kinase 4 Kinase Kd 5.84 CHEMBL
Glycogen synthase kinase-3 beta Kinase Kd 6.37 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 6.49 CHEMBL
Mitogen-activated protein kinase 9 Kinase Kd 6.04 CHEMBL
Glycogen synthase kinase-3 alpha Kinase Kd 5.28 CHEMBL
MAP kinase-activated protein kinase 2 Kinase Kd 4.83 CHEMBL
Mitogen-activated protein kinase kinase kinase MLT Kinase Kd 6.11 CHEMBL
LIM domain kinase 2 Kinase Kd 7.02 CHEMBL
Mitogen-activated protein kinase 8 Kinase Kd 5.73 CHEMBL
Mitogen-activated protein kinase kinase kinase 11 Kinase Kd 6.09 CHEMBL
Casein kinase I isoform alpha Kinase Kd 5.48 CHEMBL
Cyclin-dependent kinase 4 Kinase Kd 6.95 CHEMBL
Interleukin-1 receptor-associated kinase 1 Kinase Kd 6.61 CHEMBL
Serine/threonine-protein kinase TAO3 Kinase Kd 5.48 CHEMBL
Receptor-interacting serine/threonine-protein kinase 3 Kinase Kd 6.01 CHEMBL
Membrane-associated progesterone receptor component 1 Enzyme Kd 6.69 CHEMBL
Choline-phosphate cytidylyltransferase A Enzyme Kd 7.39 CHEMBL
Serine/threonine-protein kinase NLK Kinase Kd 6.13 CHEMBL
LIM domain kinase 1 Kinase Kd 7.58 CHEMBL

External reference:

IDSource
8L7891MRB6 UNII
C4079208 UMLSCUI
CHEMBL3301612 ChEMBL_ID
50922675 PUBCHEM_CID
DB11718 DRUGBANK_ID
D11053 KEGG_DRUG
9816 INN_ID
7908 IUPHAR_LIGAND_ID
283907 MMSL
34462 MMSL
d08817 MMSL
017615 NDDF
772091004 SNOMEDCT_US
772201002 SNOMEDCT_US
4037644 VANDF
2049106 RXNORM
C000601108 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
BRAFTOVI HUMAN PRESCRIPTION DRUG LABEL 1 70255-025 CAPSULE 75 mg ORAL NDA 32 sections
BRAFTOVI HUMAN PRESCRIPTION DRUG LABEL 1 70255-025 CAPSULE 75 mg ORAL NDA 32 sections
BRAFTOVI HUMAN PRESCRIPTION DRUG LABEL 1 70255-025 CAPSULE 75 mg ORAL NDA 32 sections
BRAFTOVI HUMAN PRESCRIPTION DRUG LABEL 1 70255-050 CAPSULE 50 mg ORAL EXPORT ONLY 1 sections
BRAFTOVI HUMAN PRESCRIPTION DRUG LABEL 1 70255-050 CAPSULE 50 mg ORAL EXPORT ONLY 1 sections