Identification
- Summary
Trametinib is a kinase inhibitor used alone or in combination with dabrafenib to treat patients with cancers with specific BRAF mutations, such as melanoma and non-small cell lung cancer.
- Brand Names
- Mekinist
- Generic Name
- Trametinib
- DrugBank Accession Number
- DB08911
- Background
Trametinib is an orally bioavailable mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2 inhibitor.4,3 It was first approved by the FDA in May 2013 for the treatment of melanoma.4 It was later approved by Health Canada on July 18, 2013 9 and by the European Commission on June 30, 2014.8 Trametinib is currently approved to treat a variety of cancers with BRAF mutations, such as non-small cell lung cancer and thyroid cancer, as monotherapy or in combination with dabrafenib, a BRAF inhibitor, for improved therapeutic efficacy. Originally developed by Japan Tobacco, trametinib was initially investigated for treating inflammation, but further studies for this indication were not pursued.4
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Trametinib (DB08911)
- Weight
- Average: 615.3948
Monoisotopic: 615.077875874 - Chemical Formula
- C26H23FIN5O4
- Synonyms
- Tramétinib
- Trametinib
- Trametinibum
- External IDs
- GSK 1120212
- GSK-1120212
- GSK1120212
- JTP 74057
- JTP-74057
Pharmacology
- Indication
Trametinib is indicated as monotherapy for the treatment of BRAF-inhibitor treatment-naïve patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations.6,8
It is used in combination with dabrafenib for the:
- treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations.7
- adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations and involvement of lymph node(s), following complete resection.7,8
- treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation.7 In Europe, it is indicated for the treatment of adults with advanced non-small cell lung cancer with a BRAF V600 mutation.8
- treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation and with no satisfactory locoregional treatment options.7
- the treatment of adult and pediatric patients six years of age and older with unresectable or metastatic solid tumours with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options. In the US, this indication is approved under accelerated approval based on the overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).7
- the treatment of pediatric patients one year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy.7
In the US, BRAF V600E or V600K mutations must be detected by an FDA-approved test. Trametinib is not indicated for the treatment of patients with colorectal cancer because of known intrinsic resistance to BRAF inhibition.7
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- Contraindications & Blackbox Warnings
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Trametinib inhibits cell growth of various BRAF V600 mutation-positive tumours in vitro and in vivo. Trametinib is often used in combination with dabrafenib, a BRAF inhibitor. In BRAF-mutant colorectal cancer, induction of EGFR-mediated MAPK pathway re-activation has been identified as a mechanism of intrinsic resistance to BRAF inhibitors.7
- Mechanism of action
The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) pathway, also known as the RAS-RAF-MEK-ERK pathway, activates a cascade of cell surface receptors and intracellular downstream signalling molecules. Activated RAS protein activates RAF, a serine/threonine kinase that activates other downstream proteins 1,5 such as mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2. MEKs then activates ERK, which works on several target proteins and nuclear transcription factors that regulate cell proliferation, differentiation, survival, and growth.1,5 ARAF, BRAF, and CRAF are three isoforms of RAF identified in humans. In particular, BRAF is known to be the most critical activator in melanoma.1,5 Certain cancers, such as melanoma, are associated with BRAF mutations, with one study suggesting that BRAF is mutated in about 50% of melanoma tumours.5 BRAF V600E and V600K mutations account for 95% of BRAF mutations.4 These BRAF mutations cause constitutive activation of the RAS-RAF-MEK-ERK pathway,7,8 leading to dysregulated proliferation and survival of tumour cells.4
Trametinib is a reversible, highly selective, allosteric inhibitor of MEK1 and MEK2.7,8 By binding to unphosphorylated MEK1 and MEK2 with high affinity, trametinib blocks the catalytic activity of MEKs.1,2,4 It also maintains MEK in an unphosphorylated form, preventing phosphorylation and activation of MEKs.1,2,4
In vitro studies suggest that dual inhibition of the MAPK pathway by MEK and B-RAF inhibitors is associated with a synergistic effect and improved therapeutic efficacy in cancers compared to using either drug alone.5 The combined use of trametinib and dabrafenib, a BRAF inhibitor, results in more significant growth inhibition of BRAF V600 mutation-positive tumour cell lines in vitro and prolonged inhibition of tumour growth in BRAF V600 mutation-positive tumour xenografts compared to either drug alone.7 The combined inhibition of MEK by trametinib and RAF by dabrafenib delays the emergence of resistance in vivo in BRAF V600 mutation-positive melanoma xenografts.8
Target Actions Organism ADual specificity mitogen-activated protein kinase kinase 1 inhibitorHumans ADual specificity mitogen-activated protein kinase kinase 2 inhibitorHumans - Absorption
Following oral administration, trametinib is rapidly and readily absorbed.5 The absorption was examined in patients with solid tumours and BRAF V600 mutation-positive metastatic melanoma. Following the administration of trametinib tablets 0.125 mg (0.0625 times the approved recommended adult dosage) to 4 mg (2 times the approved recommended adult dosage) daily, both Cmax and AUC increased dose-proportionally. Intersubject variability in AUC and Cmax at steady state is 22% and 28%, respectively.7 Trametinib accumulates with daily repeat dosing with a mean accumulation ratio of 6.0 at 2 mg once daily dose. Steady-state was achieved by Day 15.8
The mean absolute bioavailability of trametinib is 72% for oral tablets and 81% for oral solution. The Tmax is 1.5 hours. A high-fat, high-calorie meal (approximately 1000 calories) decreased trametinib AUC by 24% and Cmax by 70%, and delayed Tmax by approximately four hours as compared with fasted conditions.7
- Volume of distribution
The apparent volume of distribution (Vc/F) is 214 L.7
- Protein binding
Trametinib is 97.4% bound to human plasma proteins.7
- Metabolism
Trametinib predominantly undergoes deacetylation mediated by carboxylesterases (i.e., carboxylesterase 1b/c and 2) and other hydrolytic enzymes. The deacetylated metabolite may further be glucuronidated.8 In vitro findings suggest that deacetylation may also be accompanied by mono-oxygenation,7 hydroxylation, and glucuronidation.5 CYP3A4-mediated oxidation is a minor pathway.8 Four metabolites (M1/2/3/4) have been characterized in patients with advanced cancers. In vitro, the M1 and M3 metabolites demonstrated approximately equal or 10-fold less potent phospho-MEK1-inhibiting activity than the parent compound.5
Following a single dose of [14C]-trametinib, approximately 50% of circulating radioactivity represented the parent compound. According to findings from metabolite profiling after repeat dosing of trametinib, unchanged parent drug accounted for greater than or equal to 75% of drug-related material in plasma.7
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- Route of elimination
Following oral administration of [14C]-trametinib, greater than 80% of excreted radioactivity was recovered in the feces while less than 20% of excreted radioactivity was recovered in the urine with less than 0.1% of the excreted dose as the parent molecule.7
- Half-life
The estimated elimination half-life is 3.9 to 4.8 days.7
- Clearance
The apparent clearance is 4.9 L/h.7
- Adverse Effects
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There is no information regarding the acute toxicity (LD50) of trametinib. The highest doses of trametinib evaluated in clinical trials were 4 mg orally once daily and 10 mg administered orally once daily on two consecutive days, followed by 3 mg once daily. Out of seven patients treated on one of these two schedules, two patients experienced retinal pigment epithelial detachments.7 In clinical trials with trametinib monotherapy, one case of accidental overdose was reported from a single dose of 4 mg: no adverse events were reported in this event.8 Since trametinib is highly bound to plasma proteins, hemodialysis is likely to be ineffective in the treatment of drug overdose.7
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Trametinib which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Trametinib which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Trametinib which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Trametinib which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Trametinib which could result in a lower serum level and potentially a reduction in efficacy. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Trametinib which could result in a higher serum level. Aclidinium Aclidinium may decrease the excretion rate of Trametinib which could result in a higher serum level. Acrivastine Trametinib may decrease the excretion rate of Acrivastine which could result in a higher serum level. Acyclovir Acyclovir may decrease the excretion rate of Trametinib which could result in a higher serum level. Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Trametinib which could result in a higher serum level. 
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- Take separate from meals. Take at least 1 hour before or at least 2 hours after a meal. A high-fat, high-calorie meal decreases trametinib AUC and Cmax, and delays Tmax.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Trametinib dimethyl sulfoxide BSB9VJ5TUT 1187431-43-1 OQUFJVRYDFIQBW-UHFFFAOYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Mekinist Powder, for solution 0.05 mg/1mL Oral Novartis Pharmaceuticals Corporation 2023-03-16 Not applicable US 
Mekinist Tablet, film coated 2 mg Oral Novartis Europharm Limited 2016-10-06 Not applicable EU 
Mekinist Tablet, film coated 0.5 mg/1 Oral GlaxoSmithKline Manufacturing SpA 2013-06-17 Not applicable US Mekinist Tablet 1 mg Oral Novartis Not applicable Not applicable Canada 
Mekinist Tablet, film coated 2 mg Oral Novartis Europharm Limited 2016-09-08 Not applicable EU Mekinist Tablet, film coated 2 mg/1 Oral Novartis Pharmaceuticals Corporation 2016-03-17 2024-04-30 US Mekinist Tablet, film coated 0.5 mg Oral Novartis Europharm Limited 2016-09-08 Not applicable EU Mekinist Tablet, film coated 0.5 mg Oral Novartis Europharm Limited 2016-10-06 Not applicable EU Mekinist Tablet, film coated 2 mg/1 Oral GlaxoSmithKline Manufacturing SpA 2013-06-17 Not applicable US Mekinist Tablet, film coated 2 mg/1 Oral Novartis Pharmaceuticals Corporation 2016-03-17 Not applicable US
Categories
- ATC Codes
- L01EE01 — Trametinib
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strong)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Enzyme Inhibitors
- Kinase Inhibitor
- MAP Kinase Kinase 1, antagonists & inhibitors
- MAP Kinase Kinase 2, antagonists & inhibitors
- Mitogen-activated protein kinase (MEK) inhibitors
- Narrow Therapeutic Index Drugs
- Protein Kinase Inhibitors
- Pyridines
- Pyrimidines
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyridopyrimidines. These are compounds containing a pyridopyrimidine, which consists of a pyridine fused to a pyrimidine. Pyridine is 6-membered ring consisting of five carbon atoms and a nitrogen atom. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyridopyrimidines
- Sub Class
- Not Available
- Direct Parent
- Pyridopyrimidines
- Alternative Parents
- Acetanilides / N-acetylarylamines / Aniline and substituted anilines / Aminopyridines and derivatives / Pyrimidones / Pyridinones / Fluorobenzenes / Methylpyridines / Iodobenzenes / Aryl fluorides show 16 more
- Substituents
- Acetamide / Acetanilide / Amine / Amino acid or derivatives / Aminopyridine / Anilide / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide show 34 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- organofluorine compound, organoiodine compound, acetamides, aromatic amine, cyclopropanes, ring assembly, pyridopyrimidine (CHEBI:75998)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 33E86K87QN
- CAS number
- 871700-17-3
- InChI Key
- LIRYPHYGHXZJBZ-UHFFFAOYSA-N
- InChI
- InChI=1S/C26H23FIN5O4/c1-13-22-21(23(31(3)24(13)35)30-20-10-7-15(28)11-19(20)27)25(36)33(17-8-9-17)26(37)32(22)18-6-4-5-16(12-18)29-14(2)34/h4-7,10-12,17,30H,8-9H2,1-3H3,(H,29,34)
- IUPAC Name
- N-(3-{3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-1H,2H,3H,4H,6H,7H-pyrido[4,3-d]pyrimidin-1-yl}phenyl)acetamide
- SMILES
- CN1C(=O)C(C)=C2N(C(=O)N(C3CC3)C(=O)C2=C1NC1=CC=C(I)C=C1F)C1=CC(NC(C)=O)=CC=C1
References
- General References
- Salama AK, Kim KB: Trametinib (GSK1120212) in the treatment of melanoma. Expert Opin Pharmacother. 2013 Apr;14(5):619-27. doi: 10.1517/14656566.2013.770475. Epub 2013 Feb 23. [Article]
- Infante JR, Fecher LA, Falchook GS, Nallapareddy S, Gordon MS, Becerra C, DeMarini DJ, Cox DS, Xu Y, Morris SR, Peddareddigari VG, Le NT, Hart L, Bendell JC, Eckhardt G, Kurzrock R, Flaherty K, Burris HA 3rd, Messersmith WA: Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial. Lancet Oncol. 2012 Aug;13(8):773-81. doi: 10.1016/S1470-2045(12)70270-X. Epub 2012 Jul 16. [Article]
- Zeiser R: Trametinib. Recent Results Cancer Res. 2014;201:241-8. doi: 10.1007/978-3-642-54490-3_15. [Article]
- Wright CJ, McCormack PL: Trametinib: first global approval. Drugs. 2013 Jul;73(11):1245-54. doi: 10.1007/s40265-013-0096-1. [Article]
- Ho MY, Morris MJ, Pirhalla JL, Bauman JW, Pendry CB, Orford KW, Morrison RA, Cox DS: Trametinib, a first-in-class oral MEK inhibitor mass balance study with limited enrollment of two male subjects with advanced cancers. Xenobiotica. 2014 Apr;44(4):352-68. doi: 10.3109/00498254.2013.831143. Epub 2013 Aug 23. [Article]
- FDA Approved Drug Products: MEKINIST (trametinib) tablets, for oral use [Link]
- FDA Approved Drug Products: MEKINIST (trametinib) tablets or solution, for oral use (March 2023) [Link]
- EMA Approved Drug Products: Mekinist (trametinib) Oral Tablets [Link]
- Health Canada Approved Drug Products: MEKINIST (Trametinib) Oral Tablets [Link]
- FDA Approved Drug Products: MEKINIST (trametinib) tablets or solution, for oral use (June 2023) [Link]
- External Links
- KEGG Drug
- D10175
- PubChem Compound
- 11707110
- PubChem Substance
- 175427149
- ChemSpider
- 9881833
- BindingDB
- 50531540
- 1425099
- ChEBI
- 75998
- ChEMBL
- CHEMBL2103875
- ZINC
- ZINC000043100709
- PharmGKB
- PA166115364
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Trametinib
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Powder, for solution Oral 0.05 mg/1mL Powder, for solution Oral 4.7 mg Tablet Oral 0.5 mg Tablet Oral 1 mg Tablet Oral 2 mg Tablet, film coated Oral .5 mg/1 Tablet, film coated Oral 0.5 mg/1 Tablet, film coated Oral 1 mg/1 Tablet, film coated Oral 1 MG Tablet, film coated Oral 2 mg/1 Tablet, film coated Oral 0.5 mg Tablet, coated Oral 2 mg Tablet, film coated Oral 2 mg Tablet, coated Oral 0.5 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8703781 Yes 2014-04-22 2031-04-15 US US8835443 Yes 2014-09-16 2025-12-10 US US9271941 Yes 2016-03-01 2032-07-28 US US9155706 Yes 2015-10-13 2032-07-28 US US7378423 Yes 2008-05-27 2027-11-29 US US8580304 Yes 2013-11-12 2032-07-28 US US8952018 Yes 2015-02-10 2031-04-15 US US9399021 Yes 2016-07-26 2032-07-28 US US10869869 Yes 2020-12-22 2034-03-02 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility <1 mg/mL https://www.selleckchem.com/msds/MSDS_S2673.pdf - Predicted Properties
Property Value Source Water Solubility 0.0307 mg/mL ALOGPS logP 3.45 ALOGPS logP 3.18 Chemaxon logS -4.3 ALOGPS pKa (Strongest Acidic) 12.6 Chemaxon pKa (Strongest Basic) -3.2 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 102.06 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 156.38 m3·mol-1 Chemaxon Polarizability 55.07 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9733 Blood Brain Barrier + 0.8217 Caco-2 permeable - 0.5193 P-glycoprotein substrate Non-substrate 0.5945 P-glycoprotein inhibitor I Non-inhibitor 0.6449 P-glycoprotein inhibitor II Non-inhibitor 0.8622 Renal organic cation transporter Non-inhibitor 0.899 CYP450 2C9 substrate Non-substrate 0.7215 CYP450 2D6 substrate Non-substrate 0.8232 CYP450 3A4 substrate Substrate 0.5735 CYP450 1A2 substrate Non-inhibitor 0.8599 CYP450 2C9 inhibitor Non-inhibitor 0.5775 CYP450 2D6 inhibitor Non-inhibitor 0.9521 CYP450 2C19 inhibitor Non-inhibitor 0.8769 CYP450 3A4 inhibitor Non-inhibitor 0.836 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9337 Ames test AMES toxic 0.5498 Carcinogenicity Non-carcinogens 0.8078 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.3412 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9539 hERG inhibition (predictor II) Non-inhibitor 0.6602
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- The IC50 values for the unphosphorylated and phosphorylated forms of MEK1 are 0.7 nM and 13.2 nM, respectively.
- General Function
- Receptor signaling protein tyrosine phosphatase activity
- Specific Function
- Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones t...
- Gene Name
- MAP2K1
- Uniprot ID
- Q02750
- Uniprot Name
- Dual specificity mitogen-activated protein kinase kinase 1
- Molecular Weight
- 43438.65 Da
References
- Salama AK, Kim KB: Trametinib (GSK1120212) in the treatment of melanoma. Expert Opin Pharmacother. 2013 Apr;14(5):619-27. doi: 10.1517/14656566.2013.770475. Epub 2013 Feb 23. [Article]
- Ho MY, Morris MJ, Pirhalla JL, Bauman JW, Pendry CB, Orford KW, Morrison RA, Cox DS: Trametinib, a first-in-class oral MEK inhibitor mass balance study with limited enrollment of two male subjects with advanced cancers. Xenobiotica. 2014 Apr;44(4):352-68. doi: 10.3109/00498254.2013.831143. Epub 2013 Aug 23. [Article]
- FDA Approved Drug Products: MEKINIST (trametinib) tablets or solution, for oral use (March 2023) [Link]
- Health Canada Approved Drug Products: MEKINIST (Trametinib) Oral Tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- The IC50 values for the unphosphorylated and phosphorylated forms of MEK2 are 0.9 nM and 10.7 nM, respectively.
- General Function
- Scaffold protein binding
- Specific Function
- Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity).
- Gene Name
- MAP2K2
- Uniprot ID
- P36507
- Uniprot Name
- Dual specificity mitogen-activated protein kinase kinase 2
- Molecular Weight
- 44423.735 Da
References
- Salama AK, Kim KB: Trametinib (GSK1120212) in the treatment of melanoma. Expert Opin Pharmacother. 2013 Apr;14(5):619-27. doi: 10.1517/14656566.2013.770475. Epub 2013 Feb 23. [Article]
- FDA Approved Drug Products: MEKINIST (trametinib) tablets or solution, for oral use (March 2023) [Link]
- Health Canada Approved Drug Products: MEKINIST (Trametinib) Oral Tablets [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Trametinib is an inhibitor of CYP2C8 in vitro.
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInducer
- Curator comments
- Trametinib is an inducer of CYP3A in vitro.
- 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
- Lugowska I, Kosela-Paterczyk H, Kozak K, Rutkowski P: Trametinib: a MEK inhibitor for management of metastatic melanoma. Onco Targets Ther. 2015 Aug 25;8:2251-9. doi: 10.2147/OTT.S72951. eCollection 2015. [Article]
- FDA Approved Drug Products: MEKINIST (trametinib) tablets, for oral use [Link]
- EMA Approved Drug Products: Mekinist (trametinib) Oral Tablets [Link]
Drug created at June 24, 2013 21:36 / Updated at September 21, 2023 08:43