vemurafenib indications/contra

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
analog of PLX4720; a specific inhibitor of Raf protein kinases; used for tretment of metastatic melanoma
  • Molecular weight: 489.92
  • Formula: C23H18ClF2N3O3S
  • CLOGP: 4.17
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 2
  • TPSA: 91.92
  • ALOGS: -6.13
  • ROTB: 6

Drug dosage:

None

Approvals:

DateAgencyCompanyOrphan
Aug. 17, 2011 FDA HOFFMANN LA ROCHE

FDA Adverse Event Reporting System

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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 1698.91 51.27 512 4614 31747 3348986
Rash 1551.70 51.27 580 4546 70241 3310492
Arthralgia 939.73 51.27 389 4737 60472 3320261
Photosensitivity reaction 803.22 51.27 179 4947 3178 3377555
Metastases to central nervous system 752.85 51.27 166 4960 2797 3377936
Sunburn 602.80 51.27 111 5015 692 3380041
Fatigue 557.89 51.27 327 4799 106913 3273820
Pyrexia 553.95 51.27 296 4830 80819 3299914
Squamous cell carcinoma 514.55 51.27 119 5007 2495 3378238
Death 511.51 51.27 352 4774 151972 3228761
Hyperkeratosis 503.83 51.27 102 5024 1104 3379629
Skin papilloma 493.56 51.27 93 5033 667 3380066
Keratoacanthoma 473.31 51.27 75 5051 149 3380584
Alopecia 470.25 51.27 172 4954 18814 3361919
Diarrhoea 401.02 51.27 263 4863 104085 3276648
Decreased appetite 370.43 51.27 182 4944 41308 3339425
Nausea 353.87 51.27 265 4861 129380 3251353
Squamous cell carcinoma of skin 335.59 51.27 76 5050 1440 3379293
Melanocytic naevus 296.49 51.27 62 5064 793 3379940
Skin toxicity 288.60 51.27 65 5061 1199 3379534
Rash maculo-papular 283.41 51.27 88 5038 5779 3374954
Acute kidney injury 273.42 51.27 158 4968 49525 3331208
Erythema 267.48 51.27 130 4996 28680 3352053
Malignant melanoma 266.77 51.27 71 5055 2675 3378058
Blood lactate dehydrogenase increased 238.25 51.27 79 5047 6401 3374332
Dysphagia 235.94 51.27 106 5020 19545 3361188
Mass 233.72 51.27 62 5064 2304 3378429
Metastatic malignant melanoma 223.70 51.27 46 5080 538 3380195
Uveitis 219.23 51.27 57 5069 1956 3378777
Asthenia 213.90 51.27 150 4976 65515 3315218

Pharmacologic Action:

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SourceCodeDescription
ATC L01XE15 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Protein kinase inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000175076 Protein Kinase Inhibitors
FDA MoA N0000182138 Cytochrome P450 1A2 Inhibitors
FDA MoA N0000185503 P-Glycoprotein Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Malignant Melanoma with BRAF V600E Mutation indication
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

Acid dissociation constants calculated using MoKa v3.0.0

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

Orange Book patent data (new drug applications)

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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)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
240MG ZELBORAF HOFFMANN LA ROCHE N202429 Aug. 17, 2011 RX TABLET ORAL Aug. 17, 2018 TREATMENT OF UNRESECTABLE OR METASTATIC MELANOMA WITH THE BRAFV600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST
240MG ZELBORAF HOFFMANN LA ROCHE N202429 Aug. 17, 2011 RX TABLET ORAL Aug. 31, 2019 UPDATES MADE TO THE LABELING TO INCLUDE INFORMATION FROM STUDY MO25743 ON THE ANTI-TUMOR ACTIVITY OF VEMURAFENIB IN THE TREATMENT OF PATIENTS WITH BRAF V600E MUTATION-POSITIVE MELANOMA WITH BRAIN METASTASES
240MG ZELBORAF HOFFMANN LA ROCHE N202429 Aug. 17, 2011 RX TABLET ORAL Nov. 6, 2020 TREATMENT OF PATIENTS WITH ERDHEIM-CHESTER DISEASE WITH BRAF V600 MUTATION
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:

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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
Serine/threonine-protein kinase A-Raf Kinase IC50 6.02 CHEMBL
Vascular endothelial growth factor receptor 2 Kinase IC50 6.44 CHEMBL

External reference:

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IDSource
4030980 VUID
N0000183250 NUI
C3192263 UMLSCUI
5893 IUPHAR_LIGAND_ID
D09996 KEGG_DRUG
207SMY3FQT UNII
9286 INN_ID
CHEMBL1229517 ChEMBL_ID
DB08881 DRUGBANK_ID
1147220 RXNORM
013887 NDDF
28057 MMSL
d07798 MMSL
4030980 VANDF
N0000183250 NDFRT
702805007 SNOMEDCT_US
703656005 SNOMEDCT_US
42611257 PUBCHEM_CID
C551177 MESH_SUPPLEMENTAL_RECORD_UI
CHEBI:63637 CHEBI
032 PDB_CHEM_ID

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
ZELBORAF HUMAN PRESCRIPTION DRUG LABEL 1 50242-090 TABLET, FILM COATED 240 mg ORAL NDA 19 sections