vemurafenib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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
BA (Bioavailability) 57.80 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.473 High 0.84
caco2-efflux Caco-2 efflux ratio (BA/AB) 4.831 High 0.84
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 10.023 10^-6 cm/s High 0.84
dh-clint Dog hepatocyte intrinsic clearance 10.351 uL/min/10^6 cells High 0.84
dppb Dog plasma protein binding (% unbound) 0.270 % High 0.84
fcs-ppb Fetal calf serum protein binding (% unbound) 0.320 % High 0.84
herg hERG pIC50 5.076 pIC50 High 0.84
hh-clint Human hepatocyte intrinsic clearance 5.495 uL/min/10^6 cells High 0.84
hlm-clint Human liver microsomal intrinsic clearance 5.715 uL/min/mg protein High 0.84
hppb Human plasma protein binding (% unbound) 0.410 % High 0.84
kinase-safety-class AAK1,ABL1,ABL2,ACVR1B,ACVR2A,ACVR2B,ACVRL1,AKT1,AKT2,AKT3,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,BTK,CAMK2A,CAMK2B,CAMK2D,CAMK2G,CDK1,CDK14,CDK16,CDK19,CDK2,CDK3,CDK4,CDK5,CDK6,CDK7,CDK8,CDK9,CHEK1,CHEK2,CHUK,CLK1,CLK2,CLK4,CSF1R,CSK,DDR1,DYRK1A,DYRK1B,DYRK2,DYRK3,EGFR,EIF2AK3,EPHA2,EPHB1,EPHB3,EPHB4,ERBB2,ERBB4,FGFR1,FGFR4,FLT1,FLT3,FLT4,FYN,GAK,GRK1,GRK2,GSK3A,GSK3B,HASPIN,HIPK2,IGF1R,IKBKB,INSR,IRAK1,IRAK3,IRAK4,ITK,JAK1,JAK2,JAK3,KDR,KIT,LCK,LRRK2,LYN,MAP2K1,MAP2K4,MAP2K6,MAP2K7,MAP3K1,MAP3K10,MAP3K11,MAP3K14,MAP3K19,MAP3K2,MAP3K21,MAP3K3,MAP3K7,MAP3K8,MAP3K9,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK1,MAPK10,MAPK12,MAPK3,MAPK7,MAPK8,MAPK9,MARK1,MARK2,MARK3,MARK4,MELK,MET,MINK1,MKNK1,MKNK2,MST1R,MTOR,NTRK1,NTRK2,NTRK3,NUAK1,PAK1,PAK2,PAK4,PAK5,PDGFRB,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CD,PIK3CG,PIM1,PIM2,PIM3,PLK1,PLK2,PLK3,PLK4,PRKAA1,PRKAA2,PRKACA,PRKCA,PRKCD,PRKCI,PRKCZ,PRKD1,PRKDC,PTK2,PTK6,RET,RIPK1,RIPK3,ROCK1,ROCK2,RPS6KA1,SGK1,SIK2,SIK3,SRC,STK10,STK16,STK17A,STK3,STK33,STK4,SYK,TBK1,TEK,TGFBR1,TNIK,TNK1,TTK,TYRO3,UHMK1,ULK1,ULK2,YES1,ZAP70 184
kinase-selectivity-class AAK1,ABL2,ACVR2A,ACVR2B,ACVRL1,ALK,AURKA,AURKB,AURKC,AXL,BMX,BRAF,BTK,CAMK2A,CAMK2B,CAMK2D,CDK1,CDK16,CDK2,CDK3,CDK4,CDK6,CDK7,CDK8,CDK9,CLK2,CLK4,CSF1R,CSK,DDR1,DYRK1A,DYRK1B,DYRK3,EGFR,EIF2AK3,EPHA2,EPHB3,EPHB4,ERBB2,FGFR1,FGFR4,FLT1,FLT3,FLT4,FYN,GAK,GRK2,GSK3A,GSK3B,HIPK2,IGF1R,IRAK1,IRAK3,JAK1,JAK2,KDR,KIT,LCK,LRRK2,LYN,MAP2K1,MAP2K4,MAP2K6,MAP3K1,MAP3K10,MAP3K11,MAP3K2,MAP3K21,MAP3K7,MAP4K1,MAP4K3,MAP4K4,MAP4K5,MAPK1,MAPK11,MAPK14,MAPK7,MAPKAPK3,MARK1,MARK2,MARK3,MARK4,MELK,MET,MINK1,MST1R,NTRK1,NTRK3,NUAK1,PAK1,PAK4,PDGFRB,PDK1,PDK4,PDPK1,PIK3CA,PIK3CD,PIK3CG,PRKACA,PRKCD,PRKCZ,PRKDC,RET,RIPK3,ROCK2,SGK1,SIK2,SIK3,SRC,STK10,STK16,STK17A,STK33,STK4,SYK,TEK,TGFBR1,TNIK,TTK,TYRO3,ULK1,ULK2,YES1 123
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 46.774 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 13.459 High 0.84
mh-clint Mouse hepatocyte intrinsic clearance 25.351 High 0.84
mppb Mouse plasma protein binding (% unbound) 0.180 High 0.84
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 9.376 High 0.84
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 0.500 % High 0.84
rat-kpuu-brain Rat brain Kpuu 0.012 % High 1
rh-clint Rat hepatocyte intrinsic clearance 13.092 uL/min/10^6 cells High 0.84
rh-fuinc Rat hepatocyte fraction unbound in incubation 1.150 % High 0.84
rppb Rat plasma protein binding (% unbound) 0.160 % High 0.84
solubility-dd Solubility at pH 7.4 in DMSO 2.455 uM High 0.84

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
Disease progression 362.92 25.70 217 9229 156398 90462603
Rash 322.41 25.70 403 9043 795697 89823304
Photosensitivity reaction 281.19 25.70 95 9351 17712 90601289
Metastases to central nervous system 259.02 25.70 89 9357 17453 90601548
Skin toxicity 229.84 25.70 65 9381 6714 90612287
Keratoacanthoma 212.20 25.70 39 9407 560 90618441
Rash maculo-papular 182.98 25.70 88 9358 40845 90578156
Sunburn 180.13 25.70 46 9400 3221 90615780
Drug reaction with eosinophilia and systemic symptoms 176.34 25.70 87 9359 42671 90576330
Squamous cell carcinoma 151.98 25.70 52 9394 10049 90608952
Hyperkeratosis 141.78 25.70 45 9401 6883 90612118
Skin papilloma 133.79 25.70 41 9405 5589 90613412
Pyrexia 121.37 25.70 233 9213 660252 89958749
Erythema multiforme 120.28 25.70 46 9400 12200 90606801
Death 112.06 25.70 183 9263 456368 90162633
Arthralgia 103.86 25.70 241 9205 778281 89840720
Electrocardiogram QT prolonged 102.67 25.70 74 9372 72382 90546619
Blood lactate dehydrogenase increased 101.64 25.70 51 9395 25881 90593120
Melanocytic naevus 99.18 25.70 32 9414 5154 90613847
Squamous cell carcinoma of skin 84.12 25.70 31 9415 7418 90611583
Uveitis 82.75 25.70 38 9408 15865 90603136
Chorioretinopathy 82.45 25.70 19 9427 861 90618140
Erythema 77.68 25.70 107 9339 229139 90389862
No adverse event 77.56 25.70 61 9385 67921 90551080
Toxic skin eruption 76.82 25.70 36 9410 15738 90603263
Mass 74.16 25.70 35 9411 15542 90603459
Panniculitis 67.34 25.70 32 9414 14426 90604575
Dermatitis acneiform 66.47 25.70 25 9421 6329 90612672
Metastatic malignant melanoma 66.19 25.70 18 9428 1606 90617395
Stevens-Johnson syndrome 58.32 25.70 37 9409 29339 90589662
Neutrophilic panniculitis 56.16 25.70 9 9437 53 90618948
Malignant neoplasm progression 55.71 25.70 62 9384 106808 90512193
Diarrhoea 55.21 25.70 218 9228 938972 89680029
Solar dermatitis 53.80 25.70 10 9436 153 90618848
Keratosis pilaris 49.58 25.70 9 9437 120 90618881
Acrochordon 49.20 25.70 14 9432 1475 90617526
Drug eruption 47.48 25.70 35 9411 35372 90583629
Serous retinal detachment 45.34 25.70 11 9435 623 90618378
Face oedema 42.90 25.70 28 9418 23290 90595711
Retinal detachment 40.89 25.70 18 9428 6804 90612197
Erythema nodosum 40.56 25.70 17 9429 5707 90613294
Papilloma 40.17 25.70 9 9437 359 90618642
Myalgia 38.50 25.70 67 9379 175058 90443943
Dermatitis exfoliative 37.75 25.70 16 9430 5520 90613481
Nausea 36.34 25.70 218 9228 1110098 89508903
Decreased appetite 35.85 25.70 103 9343 376437 90242564
Drug ineffective 35.70 25.70 56 9390 1384242 89234759
Radiation skin injury 34.80 25.70 10 9436 1090 90617911
Decreased activity 34.72 25.70 17 9429 8175 90610826
Dysphagia 34.39 25.70 50 9396 112228 90506773
Condition aggravated 33.96 25.70 10 9436 595535 90023466
Hepatocellular injury 33.04 25.70 26 9420 28932 90590069
Weight increased 32.62 25.70 3 9443 417924 90201077
Enanthema 32.17 25.70 8 9438 502 90618499
Dysgeusia 31.78 25.70 33 9413 52527 90566474
Malignant melanoma in situ 31.45 25.70 9 9437 967 90618034
Impaired work ability 30.26 25.70 21 9425 19305 90599696
Palmar-plantar erythrodysaesthesia syndrome 29.49 25.70 24 9422 27999 90591002
Skin lesion 29.20 25.70 27 9419 37338 90581663
Dermatitis exfoliative generalised 27.95 25.70 13 9433 5580 90613421
Drug hypersensitivity 27.89 25.70 7 9439 463602 90155399
Nasopharyngitis 26.81 25.70 5 9441 407099 90211902
Ejection fraction decreased 26.61 25.70 22 9424 26231 90592770
Metastases to meninges 26.15 25.70 11 9435 3724 90615277

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 459.96 22.44 455 10700 276499 42333681
Disease progression 437.10 22.44 334 10821 143322 42466858
Photosensitivity reaction 402.88 22.44 144 11011 12558 42597622
Sunburn 343.77 22.44 85 11070 2030 42608150
Metastases to central nervous system 263.95 22.44 100 11055 10255 42599925
Hyperkeratosis 192.25 22.44 64 11091 4494 42605686
Skin papilloma 183.48 22.44 55 11100 2739 42607441
Skin toxicity 169.57 22.44 64 11091 6485 42603695
Squamous cell carcinoma 160.71 22.44 75 11080 12907 42597273
Keratoacanthoma 159.55 22.44 39 11116 885 42609295
Alopecia 152.18 22.44 95 11060 29181 42580999
Arthralgia 136.69 22.44 214 10941 205024 42405156
No adverse event 114.18 22.44 89 11066 38932 42571248
Uveitis 100.85 22.44 49 11106 9209 42600971
Pyrexia 98.19 22.44 274 10881 393768 42216412
Keratosis pilaris 91.83 22.44 17 11138 91 42610089
Rash maculo-papular 91.63 22.44 77 11078 37426 42572754
Melanocytic naevus 83.86 22.44 31 11124 2961 42607219
Squamous cell carcinoma of skin 70.40 22.44 43 11112 12683 42597497
Dermatitis acneiform 66.81 22.44 35 11120 7704 42602476
Mass 62.82 22.44 35 11120 8704 42601476
Chorioretinopathy 62.56 22.44 21 11134 1510 42608670
Malignant melanoma 57.79 22.44 34 11121 9366 42600814
Blood lactate dehydrogenase increased 54.49 22.44 49 11106 26032 42584148
Death 53.63 22.44 254 10901 470931 42139249
Retinopathy 50.85 22.44 20 11135 2261 42607919
Iridocyclitis 47.93 22.44 19 11136 2192 42607988
Decreased appetite 47.50 22.44 134 11021 193003 42417177
Serous retinal detachment 46.85 22.44 15 11140 929 42609251
Intentional product use issue 46.33 22.44 74 11081 71759 42538421
Drug reaction with eosinophilia and systemic symptoms 46.18 22.44 56 11099 42019 42568161
Dysphagia 45.66 22.44 74 11081 72645 42537535
Poor quality sleep 44.92 22.44 29 11126 9411 42600769
Neoplasm 44.63 22.44 25 11130 6280 42603900
Retinal detachment 43.83 22.44 25 11130 6500 42603680
Fatigue 43.21 22.44 226 10929 435415 42174765
Erythema 42.22 22.44 90 11065 108703 42501477
Metastatic malignant melanoma 39.90 22.44 17 11138 2356 42607824
Solar dermatitis 39.01 22.44 8 11147 78 42610102
Diarrhoea 38.97 22.44 229 10926 460620 42149560
Hepatotoxicity 38.79 22.44 40 11115 25127 42585053
Rash follicular 37.57 22.44 7 11148 39 42610141
Skin reaction 36.84 22.44 23 11132 7044 42603136
Toxic skin eruption 35.18 22.44 29 11126 13701 42596479
Condition aggravated 33.83 22.44 13 11142 260741 42349439
Dysgeusia 33.50 22.44 43 11112 34146 42576034
Myalgia 33.32 22.44 76 11079 96004 42514176
Decreased activity 32.69 22.44 19 11136 5116 42605064
Panniculitis 31.38 22.44 14 11141 2167 42608013
Acne 31.22 22.44 27 11128 13617 42596563
Rash papular 30.37 22.44 25 11130 11786 42598394
Impaired work ability 29.86 22.44 25 11130 12066 42598114
Blood creatine phosphokinase increased 28.71 22.44 48 11107 48290 42561890
Hyperthyroidism 28.10 22.44 26 11129 14315 42595865
Skin hypopigmentation 26.70 22.44 8 11147 397 42609783
Serous retinopathy 26.18 22.44 7 11148 229 42609951
Gamma-glutamyltransferase increased 25.94 22.44 37 11118 32460 42577720
Skin mass 25.93 22.44 16 11139 4800 42605380
Drug ineffective 25.24 22.44 83 11072 630114 41980066
Radiation skin injury 25.23 22.44 9 11146 776 42609404
Off label use 24.29 22.44 264 10891 638071 41972109
Epidermal naevus syndrome 23.99 22.44 4 11151 10 42610170
Pruritus 23.70 22.44 105 11050 188666 42421514
Product dose omission issue 23.01 22.44 6 11149 154359 42455821
Papilloma 22.95 22.44 7 11148 369 42609811
Dizziness 22.89 22.44 19 11136 249235 42360945

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 565.67 20.40 191 15921 25398 110547789
Rash 494.52 20.40 600 15512 820364 109752823
Disease progression 377.56 20.40 300 15812 243734 110329453
Skin toxicity 333.10 20.40 106 16006 11677 110561510
Keratoacanthoma 325.09 20.40 68 16044 1380 110571807
Sunburn 294.77 20.40 78 16034 4470 110568717
Rash maculo-papular 290.75 20.40 163 15949 74059 110499128
Hyperkeratosis 285.63 20.40 89 16023 9150 110564037
Squamous cell carcinoma 228.85 20.40 90 16022 18373 110554814
Pyrexia 212.79 20.40 428 15684 897837 109675350
Drug reaction with eosinophilia and systemic symptoms 187.79 20.40 128 15984 81967 110491220
Skin papilloma 166.24 20.40 55 16057 6841 110566346
Uveitis 156.32 20.40 72 16040 21638 110551549
Metastases to central nervous system 149.83 20.40 71 16041 22746 110550441
Melanocytic naevus 139.92 20.40 46 16066 5608 110567579
Keratosis pilaris 134.52 20.40 22 16090 101 110573086
Arthralgia 133.79 20.40 327 15785 779305 109793882
Chorioretinopathy 132.82 20.40 36 16076 2259 110570928
Squamous cell carcinoma of skin 129.97 20.40 59 16053 17144 110556043
Dermatitis acneiform 116.78 20.40 50 16062 12645 110560542
No adverse event 107.89 20.40 88 16024 73751 110499436
Retinal detachment 99.73 20.40 43 16069 11057 110562130
Toxic skin eruption 98.41 20.40 57 16055 27458 110545729
Death 97.99 20.40 272 15840 698597 109874590
Serous retinal detachment 95.69 20.40 26 16086 1646 110571541
Panniculitis 88.76 20.40 44 16068 15538 110557649
Erythema multiforme 87.06 20.40 48 16064 21049 110552138
Diarrhoea 81.95 20.40 355 15757 1139150 109434037
Erythema 80.86 20.40 149 15963 291298 110281889
Neutrophilic panniculitis 75.87 20.40 13 16099 83 110573104
Solar dermatitis 74.65 20.40 15 16097 247 110572940
Blood creatine phosphokinase increased 66.99 20.40 67 16045 73010 110500177
Malignant neoplasm progression 65.29 20.40 102 16010 174465 110398722
Retinopathy 63.45 20.40 24 16088 4405 110568782
Electrocardiogram QT prolonged 60.58 20.40 77 16035 108883 110464304
Papilloma 58.60 20.40 14 16098 527 110572660
Stevens-Johnson syndrome 58.41 20.40 51 16061 46850 110526337
Condition aggravated 57.21 20.40 18 16094 734818 109838369
Radiation skin injury 55.83 20.40 17 16095 1615 110571572
Iridocyclitis 55.40 20.40 23 16089 5385 110567802
Malignant melanoma 52.58 20.40 32 16080 16859 110556328
Erythema nodosum 50.82 20.40 23 16089 6630 110566557
Hepatocellular injury 49.32 20.40 48 16064 50594 110522593
Hepatotoxicity 47.15 20.40 52 16060 63348 110509839
Face oedema 47.00 20.40 39 16073 33430 110539757
Drug ineffective 46.60 20.40 95 16017 1520445 109052742
Ejection fraction decreased 46.03 20.40 42 16070 40838 110532349
Hyperthyroidism 45.10 20.40 36 16076 29225 110543962
Cholestasis 44.70 20.40 51 16061 64467 110508720
Seborrhoeic keratosis 44.65 20.40 17 16095 3175 110570012
Dermatitis exfoliative 44.58 20.40 25 16087 11322 110561865
Weight increased 43.72 20.40 5 16107 419639 110153548
Metastatic malignant melanoma 43.57 20.40 17 16095 3392 110569795
Decreased appetite 43.40 20.40 160 15952 475686 110097501
Dysgeusia 42.97 20.40 52 16060 69933 110503254
Acute kidney injury 42.42 20.40 194 15918 635236 109937951
Myalgia 41.90 20.40 97 16015 222284 110350903
Drug hypersensitivity 41.36 20.40 8 16104 454082 110119105
Infusion related reaction 41.09 20.40 4 16108 381158 110192029
Gamma-glutamyltransferase increased 40.02 20.40 47 16065 61262 110511925
Rash papular 38.38 20.40 32 16080 27607 110545580
Dizziness 37.77 20.40 28 16084 698165 109875022
Blood creatinine increased 36.92 20.40 82 16030 182807 110390380
Mass 36.49 20.40 27 16085 19603 110553584
Renal failure 36.45 20.40 93 16019 226481 110346706
Nasopharyngitis 35.80 20.40 7 16105 394354 110178833
Drug eruption 34.80 20.40 41 16071 53618 110519569
Serous retinopathy 34.42 20.40 8 16104 267 110572920
Rash follicular 33.55 20.40 7 16105 140 110573047
Acrochordon 32.84 20.40 11 16101 1419 110571768
Rheumatoid arthritis 32.67 20.40 3 16109 299610 110273577
Panniculitis lobular 32.19 20.40 6 16106 65 110573122
Dermatitis 32.12 20.40 29 16083 27808 110545379
Fall 31.61 20.40 25 16087 603457 109969730
Blood alkaline phosphatase increased 31.57 20.40 45 16067 70890 110502297
Dermal cyst 30.79 20.40 13 16099 3173 110570014
Abdominal discomfort 29.98 20.40 10 16102 393848 110179339
Dry skin 29.74 20.40 55 16057 107598 110465589
Radiation necrosis 29.66 20.40 9 16103 845 110572342
Product use issue 29.43 20.40 5 16107 311690 110261497
Palmar-plantar erythrodysaesthesia syndrome 29.38 20.40 33 16079 40992 110532195
Transaminases increased 29.38 20.40 41 16071 63349 110509838
Metastasis 29.22 20.40 17 16095 8250 110564937
Joint swelling 29.21 20.40 14 16098 442831 110130356
Skin mass 29.03 20.40 18 16094 9798 110563389
Skin reaction 28.37 20.40 24 16088 21120 110552067
Blood bilirubin increased 27.83 20.40 44 16068 75928 110497259
Intracranial tumour haemorrhage 27.66 20.40 8 16104 636 110572551
Sarcoidosis 27.28 20.40 19 16093 12560 110560627
Skin exfoliation 27.05 20.40 47 16065 87604 110485583
Maternal exposure during pregnancy 26.62 20.40 3 16109 254880 110318307
Epidermal naevus syndrome 26.33 20.40 4 16108 10 110573177
Malignant melanoma in situ 26.28 20.40 12 16100 3530 110569657
Nausea 25.83 20.40 284 15828 1235406 109337781
Dysphagia 25.68 20.40 64 16048 153536 110419651
Alopecia 25.50 20.40 113 15999 364640 110208547
Drug intolerance 25.10 20.40 14 16098 406498 110166689
Metastases to meninges 24.89 20.40 13 16099 5115 110568072
Neoplasm 24.64 20.40 17 16095 11070 110562117
Synovitis 24.58 20.40 5 16107 274087 110299100
Aspartate aminotransferase increased 24.02 20.40 64 16048 159872 110413315
Pancreatitis 23.62 20.40 46 16066 93487 110479700
Milia 23.47 20.40 5 16107 111 110573076
Skin lesion 23.34 20.40 33 16079 51598 110521589
Product dose omission issue 23.07 20.40 9 16103 321773 110251414
Fatigue 22.94 20.40 274 15838 1215684 109357503
Blood pressure increased 22.58 20.40 5 16107 258368 110314819
Rash pustular 22.41 20.40 17 16095 12812 110560375
Superficial spreading melanoma stage unspecified 22.31 20.40 6 16106 365 110572822
Autoimmune colitis 22.23 20.40 9 16103 1976 110571211
Rash morbilliform 22.05 20.40 14 16098 7937 110565250
Mobility decreased 21.99 20.40 4 16108 237418 110335769
Eosinophilia 21.83 20.40 34 16078 57902 110515285
Skin disorder 21.77 20.40 29 16083 42884 110530303
Wound 21.61 20.40 4 16108 234433 110338754
Recall phenomenon 21.58 20.40 8 16104 1388 110571799
Skin hypopigmentation 21.28 20.40 8 16104 1443 110571744
Alanine aminotransferase increased 21.28 20.40 67 16045 183706 110389481
Actinic keratosis 21.09 20.40 13 16099 7000 110566187
Acantholysis 20.86 20.40 4 16108 51 110573136
Therapeutic product effect decreased 20.81 20.40 5 16107 244311 110328876
Lower respiratory tract infection 20.66 20.40 5 16107 243101 110330086
Hypokalaemia 20.65 20.40 66 16046 182382 110390805
Acanthoma 20.65 20.40 4 16108 54 110573133
Fat necrosis 20.52 20.40 7 16105 955 110572232

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 agent
CHEBI has role CHEBI:75047 B-Raf inhibitor

Related Drugs by ATC class:

L01EC B-Raf serine-threonine kinase (BRAF) inhibitors 3 drugs
dabrafenibencorafenibtovorafenib

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)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Serine/threonine-protein kinase B-raf Kinase INHIBITOR IC50 7.68 CHEMBL CHEMBL
Serine/threonine-protein kinase Nek11 Kinase Kd 6.72 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
Muscarinic acetylcholine receptor M1 GPCR EC50 6.10 CHEMBL
Muscarinic acetylcholine receptor M2 GPCR EC50 5.80 CHEMBL
Muscarinic acetylcholine receptor M3 GPCR EC50 5.40 CHEMBL
Epidermal growth factor receptor Kinase IC50 7.32 CHEMBL
Aspartyl/asparaginyl beta-hydroxylase Enzyme IC50 4.98 CHEMBL
RAF proto-oncogene serine/threonine-protein kinase Kinase IC50 7.32 CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase IC50 8.32 CHEMBL
Vascular endothelial growth factor receptor 2 Kinase IC50 6.44 CHEMBL
Serine/threonine-protein kinase Nek2 Kinase Kd 5.30 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
Activated CDC42 kinase 1 Kinase IC50 7.72 CHEMBL
TGF-beta receptor type-2 Kinase Kd 5.47 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
Receptor-interacting serine/threonine-protein kinase 3 Kinase Kd 5.68 CHEMBL
Protein-tyrosine kinase 6 Kinase Kd 5.85 CHEMBL
Serine/threonine-protein kinase B-raf Kinase IC50 7.52 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 4 Kinase 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