Identification

Name
Vemurafenib
Accession Number
DB08881  (DB05238)
Type
Small Molecule
Groups
Approved
Description

Vemurafenib is a competitive kinase inhibitor with activity against BRAF kinase with mutations like V600E.[2] It exerts its function by binding to the ATP-binding domain of the mutant BRAF.[3] Vemurafenib was co-developed by Roche and Plexxikon and it obtained its FDA approval on August 17, 2011, under the company Hoffmann La Roche. After approval, Roche in collaboration with Genentech launched a broad development program. [8]

Structure
Thumb
Synonyms
  • BRAF(V600E) Kinase Inhibitor RO5185426
External IDs
PLX-4032 / PLX4032 / RG-7204 / RG7204 / RO-51-85426 / RO-5185426 / RO5185426
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ZelborafTablet240 mgOralHoffmann La Roche2012-03-05Not applicableCanada
ZelborafTablet, film coated240 mg/1OralGenentech, Inc.2011-08-17Not applicableUs
ZelborafTablet, film coated240 mgOralRoche Registration Gmb H2012-02-17Not applicableEu
Categories
UNII
207SMY3FQT
CAS number
918504-65-1
Weight
Average: 489.922
Monoisotopic: 489.072546264
Chemical Formula
C23H18ClF2N3O3S
InChI Key
GPXBXXGIAQBQNI-UHFFFAOYSA-N
InChI
InChI=1S/C23H18ClF2N3O3S/c1-2-9-33(31,32)29-19-8-7-18(25)20(21(19)26)22(30)17-12-28-23-16(17)10-14(11-27-23)13-3-5-15(24)6-4-13/h3-8,10-12,29H,2,9H2,1H3,(H,27,28)
IUPAC Name
N-{3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl}propane-1-sulfonamide
SMILES
CCCS(=O)(=O)NC1=C(F)C(C(=O)C2=CNC3=NC=C(C=C23)C2=CC=C(Cl)C=C2)=C(F)C=C1

Pharmacology

Indication

Vemurafenib is approved since 2011 for the treatment of metastatic melanoma with a mutation on BRAF in the valine located in the exon 15 at codon 600, this mutation is denominated as V600E.[3] The V600E mutation, a substitution of glutamic acid for valine, accounts for 54% of the cases of cutaneous melanoma.[4] Vemurafenib approval was extended in 2017, for its use as a treatment of adult patients with Erdheim-Chester Disease whose cancer cells present BRAF V600 mutation.[9] Erdheim-Chester disease is an extremely rare histiocyte cell disorder that affects large bones, large vessels, central nervous system, as well as, skin and lungs. It is reported an association of Erdheim-Chester disease and V600E mutation.[5]

Associated Conditions
Pharmacodynamics

BRAF activation results in cell growth, proliferation, and metastasis. BRAF is an intermediary molecule in MAPK whose activation depends on ERK activation, elevation of cyclin D1 and cellular proliferation. The mutation V600E produces a constitutively form of BRAF. Vemurafenib has been shown to reduce all activation markers related to BRAF; in clinical trials, vemurafenib treatment showed a reduction of cytoplasmic phosphorylated ERK and a cell proliferation driven by Ki-67. Studies also reported decrease in MAPK-related metabolic activity.[3] All the different reports indicate thet Vemurafenib generates an almost complete inhibition of the MAPK pathway.

Mechanism of action

Vemurafenib is an orally available inhibitor of mutated BRAF-serine-threonine kinase. Vemurafenif is a small molecule that interacts as a competitive inhibitor of the mutated species of BRAF. It is especially potent against the BRAF V600E mutation. Vemurafenib blocks downstream processes to inhibit tumour growth and eventually trigger apoptosis. Vemurafenib does not have antitumour effects against melanoma cell lines with the wild-type BRAF mutation.[10]

TargetActionsOrganism
ASerine/threonine-protein kinase B-raf
inhibitor
Human
Absorption

Vemurafenib is well absorbed after oral administration.[6] Peak concentrations are reached in 3 hours when an oral dose of 960 mg twice daily for 15 days has been given to patients. In the same conditions, Vemurafenib presents a Cmax of 62 mcg/ml and AUC of 601 mcg h/ml.[Label] It is unknown how food affects the absorption of vemurafenib. It presents an accumulation ratio of 7.36 after repeating doses of 960 mg [10]

Volume of distribution

The estimation of the volume of distribution for Vemurafenib is 106 L.[7]

Protein binding

Vemurafenib highly binds to plasma proteins where >99% of the administered dose will be found protein bound to serum albumin and alpha-1 acid glycoprotein.[7]

Metabolism

Vemurafenib is metabolized by CYP3A4 and the metabolites make up 5% of the components in plasma. The parent compound makes up for the remaining 95%.[7]

Route of elimination

Analysis showed that 94% of administered Vemurafenib is excreted via feces and 1% is excreted by urine.[7]

Half life

The elimination half-life of Vemurafenib is estimated to be 57 hours (range of 30-120 hours).[7]

Clearance

The total body clearance is 31 L/day.[7]

Toxicity

In the few toxicity reports, it has been shown an increased in the development of cutaneous squamous cell carcinomas or acceleration in pre-existant tumor growth.[Label]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
5'-Deoxy-5'-MethylthioadenosineThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with 5'-Deoxy-5'-Methylthioadenosine.
AbafunginThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Abafungin.
AbediterolThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Abediterol.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Vemurafenib.
AbexinostatThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Abexinostat.
AbirateroneThe serum concentration of Abiraterone can be decreased when it is combined with Vemurafenib.
AcebutololThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Acebutolol.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Vemurafenib.
AcepromazineThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Acepromazine.
AceprometazineThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Aceprometazine.
Food Interactions
Not Available

References

General References
  1. Jordan EJ, Kelly CM: Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43. doi: 10.1517/14656566.2012.737780. Epub 2012 Oct 24. [PubMed:23094782]
  2. Kim G, McKee AE, Ning YM, Hazarika M, Theoret M, Johnson JR, Xu QC, Tang S, Sridhara R, Jiang X, He K, Roscoe D, McGuinn WD, Helms WS, Russell AM, Miksinski SP, Zirkelbach JF, Earp J, Liu Q, Ibrahim A, Justice R, Pazdur R: FDA approval summary: vemurafenib for treatment of unresectable or metastatic melanoma with the BRAFV600E mutation. Clin Cancer Res. 2014 Oct 1;20(19):4994-5000. doi: 10.1158/1078-0432.CCR-14-0776. Epub 2014 Aug 5. [PubMed:25096067]
  3. Luke JJ, Hodi FS: Vemurafenib and BRAF inhibition: a new class of treatment for metastatic melanoma. Clin Cancer Res. 2012 Jan 1;18(1):9-14. doi: 10.1158/1078-0432.CCR-11-2197. Epub 2011 Nov 14. [PubMed:22083257]
  4. Schirosi L, Strippoli S, Gaudio F, Graziano G, Popescu O, Guida M, Simone G, Mangia A: Is immunohistochemistry of BRAF V600E useful as a screening tool and during progression disease of melanoma patients? BMC Cancer. 2016 Nov 18;16(1):905. [PubMed:27863476]
  5. Stempel JM, Bustamante Alvarez JG, Carpio AM, Mittal V, Dourado C: Erdheim-Chester disease, moving away from the orphan diseases: A case report. Respir Med Case Rep. 2016 Dec 3;20:55-58. eCollection 2017. [PubMed:27995058]
  6. Zhang W, Heinzmann D, Grippo JF: Clinical Pharmacokinetics of Vemurafenib. Clin Pharmacokinet. 2017 Mar 2. doi: 10.1007/s40262-017-0523-7. [PubMed:28255850]
  7. Goldinger SM, Rinderknecht J, Dummer R, Kuhn FP, Yang KH, Lee L, Ayala RC, Racha J, Geng W, Moore D, Liu M, Joe AK, Bazan SP, Grippo JF: A single-dose mass balance and metabolite-profiling study of vemurafenib in patients with metastatic melanoma. Pharmacol Res Perspect. 2015 Mar;3(2):e00113. doi: 10.1002/prp2.113. [PubMed:25729580]
  8. Roche news [Link]
  9. FDA News and Events [Link]
  10. FDA Vemurafenib application [Link]
External Links
KEGG Drug
D09996
PubChem Compound
42611257
PubChem Substance
175427131
ChemSpider
24747352
BindingDB
50396483
ChEBI
63637
ChEMBL
CHEMBL1229517
PharmGKB
PA165946873
HET
032
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Vemurafenib
ATC Codes
L01XE15 — Vemurafenib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
3og7 / 4rzv / 5hes
FDA label
Download (304 KB)
MSDS
Download (51 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentMalignant Melanoma of Skin / Melanoma (Skin) / Skin Cancers / Skin Carcinoma1
0RecruitingTreatmentPediatric Recurrent/Refractory BRAFV600E-mutant Gliomas1
1Active Not RecruitingTreatmentAdvanced Cancers2
1Active Not RecruitingTreatmentAdvanced Cancers / Advanced Malignant Neoplasm / BRAF Gene Mutation / Metastatic Malignant Neoplasm / Recurrent Malignant Neoplasm / Refractory Malignant Neoplasm1
1Active Not RecruitingTreatmentCancer, Advanced / Tumors, Solid1
1Active Not RecruitingTreatmentCarcinoma, Colorectal / Malignant Melanoma1
1Active Not RecruitingTreatmentMalignant Melanoma1
1Active Not RecruitingTreatmentMelanoma2
1Active Not RecruitingTreatmentMetastatic Melanoma, BRAF V600 Mutation Positive1
1CompletedNot AvailableMalignant Melanoma, Neoplasms2
1CompletedBasic ScienceMalignant Melanoma, Cancer1
1CompletedOtherMalignant Melanoma, Neoplasms1
1CompletedTreatmentMalignant Melanoma6
1CompletedTreatmentMalignant Melanoma, Neoplasms2
1CompletedTreatmentMelanoma1
1CompletedTreatmentMetastatic Colorectal Cancers1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentNeoplasms Malignant1
1CompletedTreatmentThyroid Cancers1
1RecruitingTreatmentMelanoma1
1RecruitingTreatmentMelanoma / Skin Cancers1
1SuspendedTreatmentAdvanced or Inoperable Malignant Melanoma With BRAF Mutation1
1TerminatedTreatmentBRAF-mutated Metastatic Melanoma / Melanoma / Metastatic Melanoma / V600EBRAF-mutated Metastatic Melanoma1
1TerminatedTreatmentMalignant Melanoma1
1TerminatedTreatmentMelanoma2
1TerminatedTreatmentMelanoma / Metastatic Cancers1
1TerminatedTreatmentRecurrent Melanoma / Stage IIIA Melanoma / Stage IIIB Melanoma / Stage IIIc Melanoma / Stage IV Melanoma / Unspecified Adult Solid Tumor, Protocol Specific1
1TerminatedTreatmentStage III or Stage IV Metastatic Melanoma That Has Not Been Previously Treated With a Selective BRAF Inhibitor / V600-mutated BRAF Metastatic Melanoma / V600-mutated BRAF Unresectable Melanoma1
1WithdrawnTreatmentBRAFV600 Mutation / Stage IV Melanoma1
1WithdrawnTreatmentMalignant Melanoma, Neoplasms1
1WithdrawnTreatmentMelanoma1
1WithdrawnTreatmentNeoplasms1
1WithdrawnTreatmentRecurrent Melanoma / Stage IV Melanoma / Tumors Metastatic to Brain1
1, 2Active Not RecruitingTreatmentMelanoma1
1, 2Active Not RecruitingTreatmentMetastatic Melanoma1
1, 2CompletedTreatmentBRAF Mutant Metastatic Melanoma1
1, 2RecruitingTreatmentMalignant Lymphomas / Tumors, Solid1
1, 2RecruitingTreatmentMelanoma3
1, 2TerminatedTreatmentAdvanced BRAF-mutant Cancers1
1, 2WithdrawnTreatmentMultiple Myeloma (MM)1
2Active Not RecruitingScreeningMetastatic Melanoma / Metastatic Melanoma, BRAF V600 Mutation Positive1
2Active Not RecruitingTreatmentColorectal Cancers1
2Active Not RecruitingTreatmentHairy Cell Leukemia (HCL)1
2Active Not RecruitingTreatmentMelanoma2
2Active Not RecruitingTreatmentMetastatic Cancers1
2Active Not RecruitingTreatmentMetastatic Melanoma1
2Active Not RecruitingTreatmentThyroid Cancers1
2CompletedTreatmentMalignant Melanoma3
2CompletedTreatmentMalignant Melanoma Stage IV1
2CompletedTreatmentMelanoma1
2CompletedTreatmentMelanoma [C04.557.465.625.650.510]1
2CompletedTreatmentMultiple Myeloma, Neoplasms1
2CompletedTreatmentNeoplasms1
2Not Yet RecruitingTreatmentMelanoma, Malignant, of Soft Parts1
2Not Yet RecruitingTreatmentMelanoma / Melanoma (Skin) / Melanoma Stage1
2Not Yet RecruitingTreatmentMetastatic Melanoma1
2RecruitingScreeningAdvanced Malignant Solid Neoplasm / Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma / Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma / Childhood Langerhans Cell Histiocytosis / Histiocytic Sarcoma (HS) / Juvenile Xanthogranuloma / Langerhans Cell Histiocytosis (LCH) / Malignant Gliomas / Malignant Lymphomas / Recurrent Central Nervous System Neoplasm / Recurrent Childhood Ependymoma / Recurrent Childhood Malignant Germ Cell Tumor / Recurrent Childhood Medulloblastoma / Recurrent Childhood Non-Hodgkin Lymphoma / Recurrent Childhood Rhabdomyosarcoma / Recurrent Childhood Soft Tissue Sarcoma / Recurrent Ewing Sarcoma / Recurrent Gliomas / Recurrent Hepatoblastoma / Recurrent Langerhans Cell Histiocytosis / Recurrent Malignant Solid Neoplasm / Recurrent Neuroblastoma / Recurrent Osteosarcoma / Recurrent Peripheral Primitive Neuroectodermal Tumor / Refractory Central Nervous System Neoplasm / Refractory Childhood Malignant Germ Cell Tumor / Refractory Langerhans cell histiocytosis / Refractory Malignant Solid Neoplasm / Refractory Neuroblastoma / Rhabdoid Tumors / Stage III Childhood Non-Hodgkin Lymphoma / Stage III Osteosarcoma / Stage III Osteosarcoma AJCC v7 / Stage III Soft Tissue Sarcoma / Stage III Soft Tissue Sarcoma AJCC v7 / Stage IV Childhood Non-Hodgkin Lymphoma / Stage IV Osteosarcoma / Stage IV Osteosarcoma AJCC v7 / Stage IV Soft Tissue Sarcoma / Stage IV Soft Tissue Sarcoma AJCC v7 / Stage IVA Osteosarcoma / Stage IVA Osteosarcoma AJCC v7 / Stage IVB Osteosarcoma / Stage IVB Osteosarcoma AJCC v7 / Wilms' tumor1
2RecruitingTreatmentAdvanced Malignant Solid Neoplasm / Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma / Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma / BRAF NP_004324.2:p.V600X / Ependymomas / Ewing's Sarcoma (ES) / Hepatoblastomas / Histiocytosis / Langerhans Cell Histiocytosis (LCH) / Malignant Germ Cell Tumor / Malignant Gliomas / Peripheral Primitive Neuroectodermal Tumor / Recurrent Childhood Central Nervous System Neoplasm / Recurrent Childhood Non-Hodgkin Lymphoma / Recurrent Malignant Solid Neoplasm / Recurrent Neuroblastoma / Refractory Central Nervous System Neoplasm / Refractory Malignant Solid Neoplasm / Refractory Neuroblastoma / Refractory Non-Hodgkin's lymphoma / Rhabdoid Tumors / Rhabdomyosarcomas / Sarcoma, Osteogenic / Soft Tissue Sarcoma (STS) / Stage III Childhood Non-Hodgkin Lymphoma / Stage IV Childhood Non-Hodgkin Lymphoma / Wilms' tumor1
2RecruitingTreatmentAdvanced Solid Tumors / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentAnaplastic Thyroid Carcinoma / Malignant Neoplasms of Thyroid and Other Endocrine Glands / Poorly Differentiated Thyroid Cancer1
2RecruitingTreatmentBRAF V600 mutation / Malignant Melanoma Stage IV / Metastatic Brain Tumors1
2RecruitingTreatmentBRAF V600E Mutation Present / Papillary Craniopharyngioma1
2RecruitingTreatmentCancer of Unknown Primary Site1
2RecruitingTreatmentCancers / Neoplasia / Neoplasms / Tumors1
2RecruitingTreatmentClinical Stage III Cutaneous Melanoma AJCC v8 / Pathologic Stage III Cutaneous Melanoma AJCC v8 / Pathologic Stage IIIA Cutaneous Melanoma AJCC v8 / Pathologic Stage IIIB Cutaneous Melanoma AJCC v8 / Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 / Pathologic Stage IIID Cutaneous Melanoma AJCC v81
2RecruitingTreatmentHairy Cell Leukemia (HCL) / Leukemias1
2RecruitingTreatmentHematologic Cancers / Metastatic Cancers / Tumors, Solid1
2RecruitingTreatmentLangerhans Cell Histiocytosis (LCH)1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2RecruitingTreatmentMalignant Melanoma2
2RecruitingTreatmentMelanoma1
2RecruitingTreatmentNeoplasms1
2RecruitingTreatmentRare Tumor / Refractory Tumors1
2RecruitingTreatmentRefractory Pediatric AML / Refractory Pediatric Solid Tumors / Relapsed Pediatric AML / Relapsed Pediatric Solid Tumors1
2SuspendedTreatmentColorectal Cancers1
2TerminatedTreatmentActive Melanoma Brain Metastases1
2TerminatedTreatmentMalignant Melanoma2
2TerminatedTreatmentMelanoma3
2TerminatedTreatmentMelanoma / Metastatic Melanoma1
2TerminatedTreatmentMetastatic Melanoma (Carrying BRAF V600 Mutation)1
2Unknown StatusTreatmentMalignant Melanoma1
2WithdrawnTreatmentStage IIIB-C Melanoma1
3Active Not RecruitingTreatmentMalignant Melanoma1
3Active Not RecruitingTreatmentMalignant Melanoma / Melanoma1
3Active Not RecruitingTreatmentMelanoma3
3CompletedTreatmentMalignant Melanoma2
3WithdrawnTreatmentMelanoma1
4Active Not RecruitingTreatmentMalignant Melanoma1
4RecruitingTreatmentNeoplasms1
Not AvailableActive Not RecruitingNot AvailableMelanoma1
Not AvailableActive Not RecruitingDiagnosticAdvanced Solid Tumors / Cancers1
Not AvailableActive Not RecruitingTreatmentThyroid Carcinoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral240 mg
Tablet, film coatedOral240 mg
Tablet, film coatedOral240 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8470818No2006-08-022026-08-02Us
US8143271No2006-06-212026-06-21Us
US7863288No2009-06-202029-06-20Us
US7504509No2006-10-222026-10-22Us
US8741920No2010-07-272030-07-27Us
US9447089No2012-06-062032-06-06Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)272°CMSDS
water solubility<1 mg/mL MSDS
logP5.1MSDS
Caco2 permeability2.9E-06FDA review
pKa7.1Royal Soc Chem
Predicted Properties
PropertyValueSource
Water Solubility0.000362 mg/mLALOGPS
logP4.95ALOGPS
logP4.62ChemAxon
logS-6.1ALOGPS
pKa (Strongest Acidic)7.17ChemAxon
pKa (Strongest Basic)3.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area91.92 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity121.97 m3·mol-1ChemAxon
Polarizability48.1 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.745
Caco-2 permeable-0.6222
P-glycoprotein substrateNon-substrate0.6215
P-glycoprotein inhibitor INon-inhibitor0.5884
P-glycoprotein inhibitor IINon-inhibitor0.699
Renal organic cation transporterNon-inhibitor0.864
CYP450 2C9 substrateNon-substrate0.7628
CYP450 2D6 substrateNon-substrate0.8038
CYP450 3A4 substrateSubstrate0.5645
CYP450 1A2 substrateInhibitor0.5762
CYP450 2C9 inhibitorInhibitor0.5987
CYP450 2D6 inhibitorNon-inhibitor0.7329
CYP450 2C19 inhibitorInhibitor0.6508
CYP450 3A4 inhibitorInhibitor0.7061
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9553
Ames testNon AMES toxic0.6323
CarcinogenicityNon-carcinogens0.7229
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5179 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6688
hERG inhibition (predictor II)Non-inhibitor0.5302
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-0024900000-4911e6c7ad52fd2c2896

Taxonomy

Description
This compound belongs to the class of organic compounds known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Aryl-phenylketones
Alternative Parents
Phenylpyridines / Sulfanilides / Pyrrolopyridines / Benzoyl derivatives / Chlorobenzenes / Fluorobenzenes / Organosulfonamides / Organic sulfonamides / Aryl chlorides / Aryl fluorides
show 12 more
Substituents
Aryl-phenylketone / 3-phenylpyridine / Sulfanilide / Pyrrolopyridine / Benzoyl / Halobenzene / Fluorobenzene / Chlorobenzene / Aryl chloride / Aryl halide
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, sulfonamide, organochlorine compound, pyrrolopyridine (CHEBI:63637)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron. Phosphorylates MAP2K1, a...
Gene Name
BRAF
Uniprot ID
P15056
Uniprot Name
Serine/threonine-protein kinase B-raf
Molecular Weight
84436.135 Da
References
  1. Jordan EJ, Kelly CM: Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43. doi: 10.1517/14656566.2012.737780. Epub 2012 Oct 24. [PubMed:23094782]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Jordan EJ, Kelly CM: Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43. doi: 10.1517/14656566.2012.737780. Epub 2012 Oct 24. [PubMed:23094782]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Jordan EJ, Kelly CM: Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43. doi: 10.1517/14656566.2012.737780. Epub 2012 Oct 24. [PubMed:23094782]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Jordan EJ, Kelly CM: Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43. doi: 10.1517/14656566.2012.737780. Epub 2012 Oct 24. [PubMed:23094782]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Vemurafenib FDA Label [File]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Mittapalli RK, Vaidhyanathan S, Sane R, Elmquist WF: Impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on the brain distribution of a novel BRAF inhibitor: vemurafenib (PLX4032). J Pharmacol Exp Ther. 2012 Jul;342(1):33-40. doi: 10.1124/jpet.112.192195. Epub 2012 Mar 27. [PubMed:22454535]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Mittapalli RK, Vaidhyanathan S, Sane R, Elmquist WF: Impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on the brain distribution of a novel BRAF inhibitor: vemurafenib (PLX4032). J Pharmacol Exp Ther. 2012 Jul;342(1):33-40. doi: 10.1124/jpet.112.192195. Epub 2012 Mar 27. [PubMed:22454535]
  2. Funck-Brentano E, Alvarez JC, Longvert C, Abe E, Beauchet A, Funck-Brentano C, Saiag P: Plasma vemurafenib concentrations in advanced BRAFV600mut melanoma patients: impact on tumour response and tolerance. Ann Oncol. 2015 Jul;26(7):1470-5. doi: 10.1093/annonc/mdv189. Epub 2015 Apr 21. [PubMed:25899783]

Drug created on May 20, 2013 00:41 / Updated on September 25, 2018 17:45