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:

None

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 429.38 29.75 57 2220 224 56289566
Neoplasm progression 153.12 29.75 55 2222 31961 56257829
Serous retinopathy 105.30 29.75 13 2264 23 56289767
Death 80.73 29.75 83 2194 341343 55948447
Retinal detachment 70.50 29.75 20 2257 5421 56284369
Off label use 65.52 29.75 95 2182 556085 55733705
Second primary malignancy 56.10 29.75 18 2259 7384 56282406
Macular detachment 45.72 29.75 7 2270 86 56289704
Hospice care 42.65 29.75 14 2263 6166 56283624
Pyrexia 41.24 29.75 66 2211 418707 55871083
Hepatic function abnormal 40.13 29.75 22 2255 34536 56255254
Disease progression 39.04 29.75 33 2244 105140 56184650
Colitis 36.23 29.75 22 2255 41789 56248001
Intestinal obstruction 33.00 29.75 18 2259 27953 56261837
Nausea 31.52 29.75 84 2193 764094 55525696
Decreased appetite 30.87 29.75 41 2236 219190 56070600

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 414.02 33.22 65 2369 476 31694434
Neoplasm progression 179.96 33.22 65 2369 20207 31674703
Serous retinopathy 105.40 33.22 16 2418 90 31694820
Death 44.60 33.22 90 2344 360479 31334431
Disease progression 44.45 33.22 44 2390 90420 31604490
Second primary malignancy 38.81 33.22 16 2418 7016 31687894
Pyrexia 35.28 33.22 74 2360 303766 31391144
Nausea 34.60 33.22 74 2360 307873 31387037

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 791.65 29.06 119 4539 753 70923033
Neoplasm progression 298.80 29.06 112 4546 45116 70878670
Serous retinopathy 203.92 29.06 29 4629 115 70923671
Death 131.86 29.06 164 4494 509897 70413889
Second primary malignancy 84.80 29.06 32 4626 13019 70910767
Off label use 78.94 29.06 159 4499 742901 70180885
Retinal detachment 78.47 29.06 27 4631 8440 70915346
Pyrexia 60.86 29.06 127 4531 606825 70316961
Hospice care 56.50 29.06 21 4637 8184 70915602
Disease progression 56.35 29.06 60 4598 156612 70767174
Uveitis 53.92 29.06 24 4634 14821 70908965
Nausea 52.83 29.06 148 4510 851940 70071846
Hepatic function abnormal 52.30 29.06 40 4618 67956 70855830
Vision blurred 50.32 29.06 45 4613 94939 70828847
Macular detachment 49.52 29.06 9 4649 197 70923589
Blood creatine phosphokinase increased 47.03 29.06 36 4622 61227 70862559
Diarrhoea 43.58 29.06 131 4527 783210 70140576
Colitis 41.47 29.06 34 4624 63780 70860006
Dermatitis acneiform 40.83 29.06 17 4641 8928 70914858
Retinopathy 35.69 29.06 12 4646 3494 70920292
Decreased appetite 32.99 29.06 66 4592 304714 70619072
Lipase increased 32.17 29.06 17 4641 15229 70908557
Amylase increased 29.24 29.06 14 4644 10194 70913592

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
C000601108 MESH_SUPPLEMENTAL_RECORD_UI
2049106 RXNORM

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 70255-050 CAPSULE 50 mg ORAL EXPORT ONLY 1 sections