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

Stem definitionDrug idCAS RN
Raf (Rapidely Accelerated Fibrosarcoma) kinase inhibitors 4185 918504-65-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • PLX-4032
  • RO 5185426
  • RG 7204
  • vemurafenib
  • zelboraf
  • Ro 51-85426
Vemurafenib is a low molecular weight, orally available inhibitor of some mutated forms of BRAF serine- threonine kinase, including BRAF V600E. Vemurafenib also inhibits other kinases in vitro such as CRAF, ARAF, wild-type BRAF, SRMS, ACK1, MAP4K5, and FGR at similar concentrations. Some mutations in the BRAF gene including V600E result in constitutively activated BRAF proteins, which can cause cell proliferation in the absence of growth factors that would normally be required for proliferation. Vemurafenib has anti-tumor effects in cellular and animal models of melanomas with mutated BRAF V600E.
  • Molecular weight: 489.92
  • Formula: C23H18ClF2N3O3S
  • CLOGP: 4.57
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 2
  • TPSA: 91.92
  • ALOGS: -6.13
  • ROTB: 6

  • Status: ONP

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

Drug dosage:

DoseUnitRoute
1.92 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ
S (Water solubility) 0.00 mg/mL Bocci G, Oprea TI, Benet LZ

Approvals:

DateAgencyCompanyOrphan
Aug. 17, 2011 FDA HOFFMANN LA ROCHE

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
Rash 314.19 25.57 386 8459 560485 62919692
Disease progression 313.32 25.57 201 8644 122557 63357620
Photosensitivity reaction 239.95 25.57 87 8758 14907 63465270
Metastases to central nervous system 239.83 25.57 84 8761 13021 63467156
Keratoacanthoma 209.28 25.57 39 8806 444 63479733
Rash maculo-papular 179.60 25.57 88 8757 31808 63448369
Sunburn 174.13 25.57 46 8799 2742 63477435
Drug reaction with eosinophilia and systemic symptoms 168.82 25.57 86 8759 33750 63446427
Skin toxicity 167.42 25.57 50 8795 4664 63475513
Squamous cell carcinoma 145.22 25.57 52 8793 8580 63471597
Hyperkeratosis 131.20 25.57 44 8801 5974 63474203
Skin papilloma 127.12 25.57 41 8804 4928 63475249
Erythema multiforme 108.70 25.57 44 8801 10125 63470052
Pyrexia 108.43 25.57 216 8629 470262 63009915
Arthralgia 97.56 25.57 232 8613 569478 62910699
Melanocytic naevus 94.47 25.57 32 8813 4476 63475701
Blood lactate dehydrogenase increased 90.47 25.57 50 8795 23066 63457111
Death 86.21 25.57 172 8673 374209 63105968
Electrocardiogram QT prolonged 85.69 25.57 69 8776 59461 63420716
Chorioretinopathy 82.99 25.57 20 8825 819 63479358
Squamous cell carcinoma of skin 81.24 25.57 31 8814 6101 63474076
Uveitis 80.81 25.57 38 8807 12515 63467662
Toxic skin eruption 70.82 25.57 35 8810 12850 63467327
Mass 68.07 25.57 35 8810 13965 63466212
Erythema 65.52 25.57 100 8745 175651 63304526
Metastatic malignant melanoma 64.78 25.57 18 8827 1297 63478880
Neutrophilic panniculitis 54.47 25.57 9 8836 47 63480130
Keratosis pilaris 54.15 25.57 9 8836 49 63480128
Stevens-Johnson syndrome 54.05 25.57 37 8808 24913 63455264
Solar dermatitis 51.73 25.57 10 8835 140 63480037
Serous retinal detachment 48.14 25.57 11 8834 356 63479821
Drug ineffective 45.98 25.57 47 8798 1044718 62435459
Panniculitis 45.56 25.57 25 8820 11360 63468817
Diarrhoea 44.63 25.57 207 8638 715159 62765018
Malignant neoplasm progression 42.91 25.57 55 8790 82066 63398111
Drug eruption 42.83 25.57 34 8811 28660 63451517
Decreased appetite 42.40 25.57 102 8743 250950 63229227
Papilloma 40.58 25.57 9 8836 254 63479923
Condition aggravated 39.10 25.57 5 8840 402212 63077965
Retinal detachment 38.20 25.57 18 8827 5951 63474226
Face oedema 36.88 25.57 27 8818 20185 63459992
Acrochordon 36.45 25.57 11 8834 1061 63479116
Erythema nodosum 35.24 25.57 16 8829 4859 63475318
Dermatitis acneiform 34.87 25.57 16 8829 4980 63475197
Decreased activity 34.22 25.57 17 8828 6303 63473874
Dermatitis exfoliative 33.52 25.57 16 8829 5443 63474734
Radiation skin injury 33.46 25.57 10 8835 933 63479244
Dysphagia 32.38 25.57 50 8795 88535 63391642
Enanthema 31.29 25.57 8 8837 418 63479759
Myalgia 29.65 25.57 64 8781 146465 63333712
Malignant melanoma in situ 29.28 25.57 9 8836 923 63479254
Dermatitis exfoliative generalised 29.13 25.57 13 8832 3794 63476383
Fall 27.79 25.57 10 8835 392324 63087853
Hepatocellular injury 27.74 25.57 26 8819 27355 63452822
Impaired work ability 26.70 25.57 21 8824 17454 63462723

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
Rash 456.17 24.43 439 10180 222313 34723999
Disease progression 447.69 24.43 321 10298 107756 34838556
Photosensitivity reaction 392.30 24.43 140 10479 10454 34935858
Sunburn 338.71 24.43 84 10535 1739 34944573
Metastases to central nervous system 268.44 24.43 99 10520 8106 34938206
Hyperkeratosis 195.17 24.43 64 10555 3685 34942627
Skin papilloma 190.83 24.43 55 10564 2048 34944264
Keratoacanthoma 162.14 24.43 38 10581 612 34945700
Squamous cell carcinoma 158.89 24.43 75 10544 11400 34934912
Alopecia 152.70 24.43 94 10525 24261 34922051
Skin toxicity 142.80 24.43 54 10565 4730 34941582
Arthralgia 138.80 24.43 211 10408 169830 34776482
Uveitis 97.42 24.43 47 10572 7488 34938824
Keratosis pilaris 92.97 24.43 17 10602 70 34946242
Pyrexia 90.69 24.43 263 10356 332750 34613562
Rash maculo-papular 87.35 24.43 71 10548 28380 34917932
Melanocytic naevus 86.74 24.43 31 10588 2313 34943999
Squamous cell carcinoma of skin 68.15 24.43 42 10577 10839 34935473
Dermatitis acneiform 66.36 24.43 34 10585 6155 34940157
Chorioretinopathy 63.87 24.43 22 10597 1471 34944841
Mass 61.23 24.43 35 10584 7870 34938442
Malignant melanoma 57.83 24.43 34 10585 8056 34938256
Blood lactate dehydrogenase increased 53.53 24.43 49 10570 22941 34923371
Iridocyclitis 50.56 24.43 19 10600 1633 34944679
Retinopathy 49.90 24.43 20 10599 2044 34944268
Drug reaction with eosinophilia and systemic symptoms 48.73 24.43 55 10564 32957 34913355
Intentional product use issue 48.23 24.43 74 10545 59742 34886570
Death 46.82 24.43 241 10378 397808 34548504
Serous retinal detachment 46.70 24.43 14 10605 598 34945714
Decreased appetite 46.54 24.43 133 10486 166259 34780053
Retinal detachment 44.80 24.43 25 10594 5366 34940946
Poor quality sleep 44.53 24.43 29 10590 8227 34938085
Neoplasm 44.48 24.43 25 10594 5442 34940870
Fatigue 43.27 24.43 224 10395 370429 34575883
Erythema 42.04 24.43 87 10532 88693 34857619
Dysphagia 41.86 24.43 71 10548 62310 34884002
Metastatic malignant melanoma 39.81 24.43 17 10602 2038 34944274
Rash follicular 39.29 24.43 7 10612 24 34946288
Impaired work ability 38.99 24.43 25 10594 6905 34939407
Dysgeusia 38.85 24.43 44 10575 26453 34919859
Solar dermatitis 38.81 24.43 8 10611 68 34946244
Skin reaction 37.43 24.43 22 10597 5208 34941104
Diarrhoea 35.16 24.43 220 10399 389692 34556620
No adverse event 33.49 24.43 38 10581 22889 34923423
Decreased activity 32.84 24.43 19 10600 4368 34941944
Acne 32.64 24.43 27 10592 11039 34935273
Hepatotoxicity 32.04 24.43 36 10583 21449 34924863
Panniculitis 30.58 24.43 14 10605 1980 34944332
Myalgia 30.35 24.43 74 10545 84036 34862276
Hyperthyroidism 29.55 24.43 25 10594 10541 34935771
Pruritus 28.23 24.43 101 10518 141880 34804432
Skin hypopigmentation 27.74 24.43 8 10611 298 34946014
Condition aggravated 27.50 24.43 12 10607 192184 34754128
Skin mass 26.53 24.43 16 10603 3969 34942343
Toxic skin eruption 25.97 24.43 24 10595 11361 34934951
Blood creatine phosphokinase increased 24.87 24.43 47 10572 44810 34901502
Serous retinopathy 24.81 24.43 6 10613 111 34946201

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
Photosensitivity reaction 502.34 21.08 178 14943 20949 79708318
Rash 496.37 21.08 576 14545 577782 79151485
Disease progression 333.26 21.08 277 14844 184085 79545182
Keratoacanthoma 317.70 21.08 66 15055 979 79728288
Sunburn 278.30 21.08 76 15045 3757 79725510
Rash maculo-papular 277.03 21.08 157 14964 55921 79673346
Hyperkeratosis 265.24 21.08 86 15035 7704 79721563
Skin toxicity 255.74 21.08 85 15036 8229 79721038
Squamous cell carcinoma 220.46 21.08 90 15031 15532 79713735
Pyrexia 187.08 21.08 402 14719 678307 79050960
Drug reaction with eosinophilia and systemic symptoms 180.99 21.08 126 14995 64118 79665149
Skin papilloma 160.58 21.08 55 15066 5831 79723436
Uveitis 149.50 21.08 70 15051 16760 79712507
Keratosis pilaris 144.14 21.08 22 15099 39 79729228
Melanocytic naevus 135.98 21.08 46 15075 4695 79724572
Metastases to central nervous system 135.92 21.08 65 15056 16310 79712957
Chorioretinopathy 133.39 21.08 38 15083 2193 79727074
Arthralgia 128.65 21.08 313 14808 571490 79157777
Squamous cell carcinoma of skin 123.51 21.08 58 15063 13975 79715292
Serous retinal detachment 96.42 21.08 25 15096 1009 79728258
Retinal detachment 96.39 21.08 43 15078 9204 79720063
Dermatitis acneiform 87.00 21.08 41 15080 9952 79719315
Toxic skin eruption 77.82 21.08 50 15071 22243 79707024
Erythema multiforme 75.34 21.08 45 15076 17606 79711661
Neutrophilic panniculitis 73.29 21.08 13 15108 77 79729190
Death 71.86 21.08 253 14868 566261 79163006
Solar dermatitis 71.71 21.08 15 15106 230 79729037
Erythema 71.29 21.08 141 14980 223149 79506118
Panniculitis 67.44 21.08 37 15084 12334 79716933
Diarrhoea 66.91 21.08 336 14785 880153 78849114
Retinopathy 60.33 21.08 24 15097 3867 79725400
Papilloma 60.07 21.08 14 15107 360 79728907
Iridocyclitis 57.96 21.08 23 15098 3681 79725586
Blood creatine phosphokinase increased 57.95 21.08 67 15054 66023 79663244
Condition aggravated 56.39 21.08 13 15108 501111 79228156
Malignant neoplasm progression 56.14 21.08 96 15025 135894 79593373
Electrocardiogram QT prolonged 55.95 21.08 77 15044 90309 79638958
Radiation skin injury 53.58 21.08 17 15104 1417 79727850
Stevens-Johnson syndrome 52.83 21.08 50 15071 39116 79690151
Drug ineffective 50.22 21.08 80 15041 1080833 78648434
Erythema nodosum 49.95 21.08 23 15098 5294 79723973
Decreased appetite 48.63 21.08 159 14962 342259 79387008
Malignant melanoma 46.41 21.08 31 15090 14710 79714557
Hyperthyroidism 43.36 21.08 35 15086 22174 79707093
Cholestasis 42.64 21.08 51 15070 52058 79677209
Metastatic malignant melanoma 42.10 21.08 17 15104 2846 79726421
Face oedema 41.98 21.08 38 15083 28098 79701169
Seborrhoeic keratosis 41.68 21.08 16 15105 2344 79726923
Hepatocellular injury 41.30 21.08 48 15073 47545 79681722
Ejection fraction decreased 40.75 21.08 41 15080 34536 79694731
Dermatitis exfoliative 39.56 21.08 25 15096 10804 79718463
Fall 39.04 21.08 22 15099 487607 79241660
Dysgeusia 38.86 21.08 51 15070 57126 79672141
Dizziness 36.40 21.08 28 15093 526413 79202854
Weight increased 35.91 21.08 5 15116 277381 79451886
Hepatotoxicity 35.20 21.08 46 15075 51306 79677961
Alopecia 35.13 21.08 110 15011 231245 79498022
Drug hypersensitivity 35.12 21.08 7 15114 298909 79430358
Gamma-glutamyltransferase increased 34.45 21.08 47 15074 54633 79674634
Myalgia 33.65 21.08 94 15027 185547 79543720
Acute kidney injury 33.61 21.08 190 14931 519214 79210053
Rash follicular 33.30 21.08 7 15114 110 79729157
Radiation necrosis 33.11 21.08 9 15112 436 79728831
Mass 32.98 21.08 27 15094 17445 79711822
Skin exfoliation 32.67 21.08 46 15075 55054 79674213
Panniculitis lobular 32.36 21.08 6 15115 47 79729220
Sarcoidosis 32.35 21.08 20 15101 8315 79720952
Dry skin 32.07 21.08 51 15070 67944 79661323
Serous retinopathy 31.08 21.08 7 15114 154 79729113
Dermatitis 30.25 21.08 28 15093 21293 79707974
Infusion related reaction 30.15 21.08 4 15117 230233 79499034
Blood creatinine increased 29.57 21.08 80 15041 154977 79574290
Drug eruption 29.56 21.08 39 15082 43896 79685371
Dermal cyst 29.42 21.08 13 15108 2719 79726548
Blood pressure increased 29.35 21.08 3 15118 211357 79517910
Renal failure 28.18 21.08 93 15028 200875 79528392
Skin mass 27.92 21.08 18 15103 8045 79721222
Rash papular 27.70 21.08 27 15094 21889 79707378
Nasopharyngitis 27.70 21.08 7 15114 253874 79475393
Malignant melanoma in situ 27.48 21.08 12 15109 2440 79726827
Intracranial tumour haemorrhage 27.05 21.08 8 15113 527 79728740
Product dose omission issue 26.67 21.08 7 15114 247530 79481737
Skin reaction 26.55 21.08 23 15098 16045 79713222
Palmar-plantar erythrodysaesthesia syndrome 26.40 21.08 32 15089 33102 79696165
Joint swelling 26.15 21.08 11 15110 288635 79440632
Metastases to meninges 25.99 21.08 13 15108 3588 79725679
Metastasis 25.42 21.08 16 15105 6864 79722403
Epidermal naevus syndrome 25.27 21.08 4 15117 10 79729257
BRAF gene mutation 24.89 21.08 5 15116 62 79729205
Toxicity to various agents 24.83 21.08 26 15095 421514 79307753
Transaminases increased 24.66 21.08 39 15082 51704 79677563
Milia 23.88 21.08 5 15116 77 79729190
Blood alkaline phosphatase increased 23.73 21.08 43 15078 63621 79665646
Vogt-Koyanagi-Harada disease 23.12 21.08 6 15115 243 79729024
Rash erythematous 22.79 21.08 40 15081 57729 79671538
Pancreatitis 22.67 21.08 44 15077 68531 79660736
Dysphagia 22.26 21.08 62 15059 122074 79607193
Dermatitis exfoliative generalised 22.25 21.08 15 15106 7226 79722041
Acantholysis 22.23 21.08 4 15117 26 79729241
Skin hypopigmentation 22.17 21.08 8 15113 987 79728280
Superficial spreading melanoma stage unspecified 22.05 21.08 6 15115 292 79728975
Abdominal discomfort 22.00 21.08 10 15111 250717 79478550
Rash morbilliform 21.97 21.08 14 15107 6136 79723131
General physical health deterioration 21.39 21.08 106 15015 275132 79454135
Eosinophilia 21.36 21.08 34 15087 45311 79683956
Neoplasm 21.34 21.08 16 15105 9100 79720167
Fatigue 21.25 21.08 269 14852 929458 78799809
Hepatitis 21.23 21.08 38 15083 55689 79673578
Recall phenomenon 21.13 21.08 8 15113 1129 79728138
Skin disorder 21.11 21.08 29 15092 33914 79695353

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EC01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
B-Raf serine-threonine kinase (BRAF) inhibitors
FDA MoA N0000175076 Protein Kinase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000182138 Cytochrome P450 1A2 Inhibitors
FDA MoA N0000185503 P-Glycoprotein Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agents
CHEBI has role CHEBI:75047 BRAF inhibitors

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

DiseaseRelationSNOMED_IDDOID
Erdheim-Chester Disease indication 699537002 DOID:4329
Malignant Melanoma with BRAF V600E Mutation indication 830150003
Hypocalcemia contraindication 5291005
Hyperbilirubinemia contraindication 14783006 DOID:2741
Torsades de pointes contraindication 31722008
Hypokalemia contraindication 43339004
Bradycardia contraindication 48867003
Acute nephropathy contraindication 58574008
Iritis contraindication 65074000 DOID:1406
Prolonged QT interval contraindication 111975006
Uveitis contraindication 128473001 DOID:13141
Liver function tests abnormal contraindication 166603001
Hypomagnesemia contraindication 190855004
Pregnancy, function contraindication 289908002
Breastfeeding (mother) contraindication 413712001
Decompensated chronic heart failure contraindication 424404003
Congenital long QT syndrome contraindication 442917000
Retinal Blood Vessel Occlusions contraindication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 7.98 acidic
pKa2 13.65 acidic
pKa3 4.56 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
240MG ZELBORAF HOFFMANN LA ROCHE N202429 Aug. 17, 2011 RX TABLET ORAL 8470818 Aug. 2, 2026 TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAFV600E MUTATION AS DETECTED BY AN FDA APPROVED TEST
240MG ZELBORAF HOFFMANN LA ROCHE N202429 Aug. 17, 2011 RX TABLET ORAL 8470818 Aug. 2, 2026 ZELBORAF IS INDICATED FOR THE TREATMENT OF PATIENTS WITH ERDHEIM-CHESTER DISEASE WITH BRAF V600 MUTATION

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
240MG ZELBORAF HOFFMANN LA ROCHE N202429 Aug. 17, 2011 RX TABLET ORAL Nov. 6, 2024 TREATMENT OF PATIENTS WITH ERDHEIM-CHESTER DISEASE WITH BRAF V600 MUTATION

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Serine/threonine-protein kinase B-raf Kinase INHIBITOR IC50 7.68 CHEMBL CHEMBL
RAF proto-oncogene serine/threonine-protein kinase Kinase IC50 7.32 CHEMBL
Vascular endothelial growth factor receptor 2 Kinase IC50 6.44 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 5 Kinase Kd 5.75 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 6.37 CHEMBL
TGF-beta receptor type-2 Kinase Kd 5.47 CHEMBL
Protein-tyrosine kinase 6 Kinase Kd 5.85 CHEMBL
Mitogen-activated protein kinase kinase kinase MLT Kinase IC50 7.64 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5 Kinase Kd 6.13 CHEMBL
Serine/threonine-protein kinase A-Raf Kinase IC50 6.02 CHEMBL
GTPase KRas Enzyme IC50 4.78 CHEMBL
Ferrochelatase, mitochondrial Enzyme EC50 5.30 CHEMBL
Receptor-interacting serine/threonine-protein kinase 3 Kinase Kd 5.68 CHEMBL
Aspartyl/asparaginyl beta-hydroxylase Enzyme IC50 4.98 CHEMBL
Serine/threonine-protein kinase B-raf Kinase IC50 7.52 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 4 Unclassified Kd 8.09 CHEMBL

External reference:

IDSource
4030980 VUID
N0000183250 NUI
D09996 KEGG_DRUG
4030980 VANDF
C3192263 UMLSCUI
CHEBI:63637 CHEBI
032 PDB_CHEM_ID
CHEMBL1229517 ChEMBL_ID
D000077484 MESH_DESCRIPTOR_UI
DB08881 DRUGBANK_ID
5893 IUPHAR_LIGAND_ID
9286 INN_ID
207SMY3FQT UNII
42611257 PUBCHEM_CID
1147220 RXNORM
185260 MMSL
28057 MMSL
d07798 MMSL
013887 NDDF
702805007 SNOMEDCT_US
703656005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ZELBORAF HUMAN PRESCRIPTION DRUG LABEL 1 50242-090 TABLET, FILM COATED 240 mg ORAL NDA 29 sections
ZELBORAF HUMAN PRESCRIPTION DRUG LABEL 1 50242-090 TABLET, FILM COATED 240 mg ORAL NDA 29 sections