Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C23H18ClF2N3O3S |
| Molecular Weight | 489.922 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCS(=O)(=O)NC1=C(F)C(C(=O)C2=CNC3=C2C=C(C=N3)C4=CC=C(Cl)C=C4)=C(F)C=C1
InChI
InChIKey=GPXBXXGIAQBQNI-UHFFFAOYSA-N
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)
| Molecular Formula | C23H18ClF2N3O3S |
| Molecular Weight | 489.922 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
Vemurafenib (trade name Zelboraf) is a low molecular weight, orally available kinase inhibitor. It inhibits of some mutated forms of BRAF serinethreonine kinase, including BRAF V600E and is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. Vemurafenib also inhibits other kinases in vitro such as CRAF, ARAF, wild-type BRAF, SRMS, ACK1, MAP4K5 and FGR at similar concentrations. Vemurafenib is not recommended for use in patients with wild-type BRAF melanoma. Zelboraf does not cure melanoma, but stops it's progression. Some 26% of patients in clinical trials developed a non melanoma form of skin cancer called cutaneous squamous cell carcinoma, which can usually be removed via relatively simple surgery. Other side effects include joint pain, rash, hair loss, fatigue, nausea, and skin sensitivity to sunlight. Patients taking Zelboraf must avoid sun exposure. It's not yet clear how long Zelboraf can increase melanoma survival.
CNS Activity
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas. | 2010 Dec |
|
| Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. | 2010 Sep 30 |
|
| The BRAFT1799A mutation confers sensitivity of thyroid cancer cells to the BRAFV600E inhibitor PLX4032 (RG7204). | 2011 Jan 28 |
|
| Novel immunotherapeutic agents and small molecule antagonists of signalling kinases for the treatment of metastatic melanoma. | 2011 Jul 9 |
|
| Improved survival with vemurafenib in melanoma with BRAF V600E mutation. | 2011 Jun 30 |
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| Overcoming metastatic melanoma with BRAF inhibitors. | 2011 May |
|
| BRAF targeted therapy changes the treatment paradigm in melanoma. | 2011 May 24 |
|
| New drugs in melanoma: it's a whole new world. | 2011 Sep |
|
| Vemurafenib for the treatment of melanoma. | 2012 Dec |
|
| Conformation-specific effects of Raf kinase inhibitors. | 2012 Sep 13 |
|
| A multisite blinded study for the detection of BRAF mutations in formalin-fixed, paraffin-embedded malignant melanoma. | 2013 |
|
| BRAF inhibitor activity in V600R metastatic melanoma. | 2013 Mar |
|
| Characterization of vemurafenib phototoxicity in a mouse model. | 2014 Jan |
|
| Identification of recurrent SMO and BRAF mutations in ameloblastomas. | 2014 Jul |
|
| Copper is required for oncogenic BRAF signalling and tumorigenesis. | 2014 May 22 |
|
| Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells. | 2015 Aug 18 |
|
| The quinone methide aurin is a heat shock response inducer that causes proteotoxic stress and Noxa-dependent apoptosis in malignant melanoma cells. | 2015 Jan 16 |
|
| Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. | 2015 May 18 |
|
| Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers. | 2015 Sep 14 |
Patents
Sample Use Guides
960 mg twice daily. Administer ZELBORAF approximately 12 hours apart with or without a meal. Management of symptomatic adverse drug reactions may require dose reduction, treatment interruption, or treatment discontinuation of ZELBORAF. Dose reductions resulting in a dose below 480 mg twice daily are not recommended
Route of Administration:
Oral
The antitumor effects of vemurafenib against SM1 cells were tested by in vitro MTS cell proliferation assay after 72 hours of treatment. The IC50 of vemurafenib was 14 uM, which is approximately one log higher than the sensitivity of M229 (IC50 of 0.5 uM), a BRAF V600E mutant human melanoma cell line highly sensitive to vemurafenib, and at a similar range as the relatively resistant BRAF V600E mutant human melanoma cell line M233 (IC50 of 15 uM).
| Substance Class |
Chemical
Created
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admin
on
Edited
Mon Oct 21 20:54:17 UTC 2019
by
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on
Mon Oct 21 20:54:17 UTC 2019
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| Record UNII |
207SMY3FQT
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| Record Status |
Validated (UNII)
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| Record Version |
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| Classification Tree | Code System | Code | ||
|---|---|---|---|---|
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FDA ORPHAN DRUG |
325310
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FDA ORPHAN DRUG |
444114
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NCI_THESAURUS |
C129825
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FDA ORPHAN DRUG |
399213
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EMA ASSESSMENT REPORTS |
ZELBORAF (AUTHORIZED: MELANOMA)
Created by
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EU-Orphan Drug |
EU/3/17/1846
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NDF-RT |
N0000175605
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WHO-VATC |
QL01XE15
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LIVERTOX |
1024
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FDA ORPHAN DRUG |
529616
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NCI_THESAURUS |
C2189
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FDA ORPHAN DRUG |
444314
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WHO-ATC |
L01XE15
Created by
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| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
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5893
Created by
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PRIMARY | |||
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918504-65-1
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PRIMARY | |||
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1147220
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PRIMARY | RxNorm | ||
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SUB32161
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PRIMARY | |||
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N0000185503
Created by
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PRIMARY | P-Glycoprotein Inhibitors [MoA] | ||
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42611257
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PRIMARY | |||
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M11408
Created by
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PRIMARY | Merck Index | ||
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9286
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PRIMARY | |||
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C64768
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PRIMARY | |||
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CHEMBL1229517
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PRIMARY | |||
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C551177
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PRIMARY | |||
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918504-65-1
Created by
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PRIMARY | |||
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918504-65-1
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PRIMARY | |||
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918504-65-1
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PRIMARY | |||
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DB08881
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PRIMARY | |||
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N0000182138
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PRIMARY | Cytochrome P450 1A2 Inhibitors [MoA] | ||
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VEMURAFENIB
Created by
admin on Mon Oct 21 20:54:17 UTC 2019 , Edited by admin on Mon Oct 21 20:54:17 UTC 2019
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PRIMARY |
| Related Record | Type | Details | ||
|---|---|---|---|---|
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EXCRETED UNCHANGED |
From the human mass balance trial (NP25158), the mean percent of 14 C-vemurafenib related material recovered in feces and urine within 432 hrs pos t-dose was 94.1% and 0.97%, respectively.
FECAL
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TRANSPORTER -> INHIBITOR |
MDCKII- MDR1 cells.
IC50
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TARGET -> INHIBITOR | |||
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BINDER->LIGAND |
BINDING
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EXCRETED UNCHANGED |
From the human mass balance trial (NP25158), the mean percent of 14 C-vemurafenib related material recovered in feces and urine within 432 hrs pos t-dose was 94.1% and 0.97%, respectively.
URINE
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TRANSPORTER -> SUBSTRATE | |||
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TARGET -> INHIBITOR |
COMPETITIVE INHIBITOR
IC50
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METABOLIC ENZYME -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR |
MDCKII- MDR1 cells.
IC50
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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ACTIVE MOIETY |
FECAL; URINE
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| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
|---|---|---|---|---|---|---|
| Tmax | PHARMACOKINETIC |
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| Volume of Distribution | PHARMACOKINETIC |
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| Biological Half-life | PHARMACOKINETIC |
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