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Identification
- Summary
Binimetinib is a medication used to treat metastatic melanoma with specific mutations.
- Brand Names
- Mektovi
- Generic Name
- Binimetinib
- DrugBank Accession Number
- DB11967
- Background
Binimetinib, also known as Mektovi, is a potent and selective oral mitogen-activated protein kinase 1/2 (MEK 1/2) inhibitor which is combined with Encorafenib.2,4
On June 27, 2018, the Food and Drug Administration approved the combination of Encorafenib and binimetinib (BRAFTOVI and MEKTOVI, from Array BioPharma Inc.) in combination for patients with unresectable or metastatic melanoma with the BRAF V600E or V600K mutations, as detected by an FDA-approved test.4
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Binimetinib (DB11967)
- Weight
- Average: 441.233
Monoisotopic: 440.02956 - Chemical Formula
- C17H15BrF2N4O3
- Synonyms
- Binimetinib
- External IDs
- ARRY-162
- ARRY-438162
- MEK-162
- MEK162
- NVP-MEK162
Pharmacology
- Indication
Binimetinib, in conjunction with encorafenib, is indicated for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutation and metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation.5
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Metastatic melanoma Regimen in combination with: Encorafenib (DB11718) •••••••••••• •••••• Used in combination to treat Metastatic melanoma Regimen in combination with: Encorafenib (DB11718) •••••••••••• •••••• Used in combination to treat Metastatic non-small cell lung cancer Regimen in combination with: Encorafenib (DB11718) •••••••••••• ••••• •••••• Used in combination to treat Unresectable melanoma Regimen in combination with: Encorafenib (DB11718) •••••••••••• •••••• Used in combination to treat Unresectable melanoma Regimen in combination with: Encorafenib (DB11718) •••••••••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
In vitro, binimetinib inhibited extracellular signal-related kinase (ERK) phosphorylation in cell-free assays as well as viability and MEK-dependent phosphorylation of BRAF-mutant human melanoma cell lines. Binimetinib also inhibited in vivo ERK phosphorylation and tumor growth in BRAF-mutant murine xenograft models.5 MEK is an enzyme that regulates the biosynthesis of inflammatory cytokines such as TNF, IL-6 and IL-1; therefore, binimetinib anti-tumor activity can be mediated through the interference of cytokines biosynthesis.1,3
Binimetinib and encorafenib target two different kinases in the RAS/RAF/MEK/ERK pathway. Compared to either drug alone, coadministration of encorafenib and binimetinib resulted in greater anti-proliferative activity in vitro in BRAF mutation-positive cell lines and greater anti-tumor activity with respect to tumor growth inhibition in BRAF V600E mutant human melanoma xenograft studies in mice. Additionally, the combination of binimetinib and encorafenib delayed the emergence of resistance in BRAF V600E mutant human melanoma xenografts in mice compared to either drug alone. In a BRAF V600E mutant NSCLC patient-derived xenograft model in mice, coadministration of encorafenib and binimetinib resulted in greater anti-tumor activity compared to binimetinib alone, with respect to tumor growth inhibition. Increased tumor growth delay after dosing cessation was also observed with the coadministration compared to either drug alone.5
Following MEKTOVI 45 mg twice daily, no clinically meaningful QT prolongation was observed.5
- Mechanism of action
Binimetinib, noncompetitive with ATP, binds reversibly to and inhibits the activity of mitogen-activated extracellular signal-regulated kinase (MEK) 1 and 2. The inhibition of MEK1/2 prevents the activation of MEK1/2-dependent effector proteins and transcription factors, resulting in the inhibition of growth factor-mediated cell signaling such as the downstream extracellular signal-related kinase (ERK) pathway. This may lead to the inhibition of tumor cell proliferation and an inhibition in the production of various inflammatory cytokines including interleukin-1, -6, and tumor necrosis factor. MEK1/2 are themselves threonine and tyrosine kinases that possess a dual specificity. They subsequently contribute critically to the activation of the RAS/RAF/MEK/ERK pathway and are typically upregulated in a number of different tumor cell types.3,5
Target Actions Organism ADual specificity mitogen-activated protein kinase kinase 2 inhibitorHumans ADual specificity mitogen-activated protein kinase kinase 1 inhibitorHumans - Absorption
The pharmacokinetics of binimetinib was studied in healthy subjects and patients with solid tumors. After twice-daily dosing, the accumulation is 1.5-fold and the coefficient of variation (CV%) of the area under the concentration-time curve (AUC) is <40% at steady state. The systemic exposure of binimetinib is approximately dose proportional.5
After oral administration, at least 50% of the binimetinib dose was absorbed with a median time to maximum concentration (Tmax) of 1.6 hours.5
The administration of a single dose of binimetinib 45 mg with a high-fat, high-calorie meal (consisting of approximately 150 calories from protein, 350 calories from carbohydrate, and 500 calories from fat) in healthy subjects had no effect on binimetinib exposure.5
- Volume of distribution
The geometric mean (CV%) of the apparent volume of distribution of binimetinib is 92 L (45%).5
- Protein binding
Binimetinib is 97% bound to human plasma proteins and the blood-to-plasma ratio is 0.72.5
- Metabolism
The primary metabolic pathway is glucuronidation with UGT1A1 contributing up to 61% of the binimetinib metabolism. Other pathways of binimetinib metabolism include N-dealkylation, amide hydrolysis, and loss of ethane-diol from the side chain. The active metabolite M3 produced by CYP1A2 and CYP2C19 represents 8.6% of the binimetinib exposure. Following a single oral dose of 45 mg radiolabeled binimetinib, approximately 60% of the circulating radioactivity AUC in plasma was attributable to binimetinib.5
- Route of elimination
Following a single oral dose of 45 mg radiolabeled binimetinib in healthy subjects, 62% (32% unchanged) of the administered dose was recovered in the feces while 31% (6.5% unchanged) was recovered in the urine.5
- Half-life
The mean (CV%) terminal half-life (t1/2) of binimetinib is 3.5 hours (28.5%).5
- Clearance
The apparent clearance (CL/F) of binimetinib is is 20.2 L/h (24%).5
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Based on findings from animal reproduction studies and its mechanism of action, binimetinib can cause fetal harm when administered to a pregnant woman. There are no available clinical data on the use of binimetinib during pregnancy. In animal reproduction studies, oral administration of binimetinib during the period of organogenesis was embryotoxic and an abortifacient in rabbits at doses greater than or equal to those resulting in exposures approximately 5 times the human exposure at the clinical dose of 45 mg twice daily. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.5
No overall differences in the safety or effectiveness of MEKTOVI plus encorafenib were observed in older patients as compared to younger patients.5
Since binimetinib is 97% bound to plasma proteins, hemodialysis is likely to be ineffective in the treatment of overdose with binimetinib.5
Carcinogenicity studies with binimetinib have not been conducted. Binimetinib was not genotoxic in studies evaluating reverse mutations in bacteria, chromosomal aberrations in mammalian cells, or micronuclei in the bone marrow of rats.5
- 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 softwareAbametapir The serum concentration of Binimetinib can be increased when it is combined with Abametapir. Abatacept The metabolism of Binimetinib can be increased when combined with Abatacept. Abemaciclib Abemaciclib may decrease the excretion rate of Binimetinib which could result in a higher serum level. Abiraterone The serum concentration of Binimetinib can be increased when it is combined with Abiraterone. Abrocitinib The serum concentration of Binimetinib can be increased when it is combined with Abrocitinib. - Food Interactions
- Take with or without food.
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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Mektovi Tablet, film coated 15 mg Oral Pierre Fabre Médicament 2020-12-16 Not applicable EU 
Mektovi Tablet, film coated 15 mg/1 Oral Array BioPharma Inc. 2018-06-27 Not applicable US 
Mektovi Tablet, film coated 15 mg Oral Pierre Fabre Médicament 2020-12-16 Not applicable EU Mektovi Tablet 15 mg Oral Pfizer Canada Ulc 2021-07-05 Not applicable Canada 
Categories
- ATC Codes
- L01EE03 — Binimetinib
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Heterocyclic Compounds, Fused-Ring
- Kinase Inhibitor
- MAP Kinase Kinase 1, antagonists & inhibitors
- MAP Kinase Kinase 2, antagonists & inhibitors
- Mitogen-activated protein kinase (MEK) inhibitors
- Narrow Therapeutic Index Drugs
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Protein Kinase Inhibitors
- UGT1A1 Substrates
- UGT1A1 Substrates with a Narrow Therapeutic Index
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 3-halobenzoic acids and derivatives. These are benzoic acids or derivatives carrying a halogen atom at the 3-position of the benzene ring.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Benzoic acids and derivatives
- Direct Parent
- 3-halobenzoic acids and derivatives
- Alternative Parents
- Benzimidazoles / Aniline and substituted anilines / Fluorobenzenes / Bromobenzenes / Primary aromatic amines / Aryl bromides / Aryl fluorides / N-substituted imidazoles / Vinylogous amides / Heteroaromatic compounds show 8 more
- Substituents
- 3-halobenzoic acid or derivatives / Alcohol / Amine / Amino acid or derivatives / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Aryl bromide / Aryl fluoride / Aryl halide / Azacycle show 23 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 181R97MR71
- CAS number
- 606143-89-9
- InChI Key
- ACWZRVQXLIRSDF-UHFFFAOYSA-N
- InChI
- InChI=1S/C17H15BrF2N4O3/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26)
- IUPAC Name
- 5-[(4-bromo-2-fluorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-1,3-benzodiazole-6-carboxamide
- SMILES
- CN1C=NC2=C(F)C(NC3=CC=C(Br)C=C3F)=C(C=C12)C(=O)NOCCO
References
- General References
- Koelblinger P, Dornbierer J, Dummer R: A review of binimetinib for the treatment of mutant cutaneous melanoma. Future Oncol. 2017 Aug;13(20):1755-1766. doi: 10.2217/fon-2017-0170. Epub 2017 Jun 7. [Article]
- Bendell JC, Javle M, Bekaii-Saab TS, Finn RS, Wainberg ZA, Laheru DA, Weekes CD, Tan BR, Khan GN, Zalupski MM, Infante JR, Jones S, Papadopoulos KP, Tolcher AW, Chavira RE, Christy-Bittel JL, Barrett E, Patnaik A: A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. Br J Cancer. 2017 Feb 28;116(5):575-583. doi: 10.1038/bjc.2017.10. Epub 2017 Feb 2. [Article]
- Cancer.gov link [Link]
- FDA approves encorafenib and binimetinib in combination for unresectable or metastatic melanoma with BRAF mutations [Link]
- FDA Approved Drug Products: MEKTOVI® (binimetinib) tablets, for oral use [Link]
- Binimetinib [File]
- EMA assessment [File]
- External Links
- Human Metabolome Database
- HMDB0304890
- PubChem Compound
- 10288191
- PubChem Substance
- 347828291
- ChemSpider
- 8463660
- ChEBI
- 145371
- ChEMBL
- CHEMBL3187723
- ZINC
- ZINC000038460704
- PharmGKB
- PA166179867
- PDBe Ligand
- QO7
- Wikipedia
- Binimetinib
- PDB Entries
- 7m0u
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data4 Recruiting Treatment Solid Tumors 1 somestatus stop reason just information to hide 3 Active Not Recruiting Treatment Melanoma 3 somestatus stop reason just information to hide 3 Completed Treatment BRAF V600E-mutant Metastatic Colorectal Cancer 1 somestatus stop reason just information to hide 3 Completed Treatment Metastatic or Unresectable Cutaneous Melanoma 1 somestatus stop reason just information to hide 3 Recruiting Treatment Biliary Tract Neoplasms 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 15 mg Tablet Oral 15.000 mg Tablet, film coated Oral 15 mg/1 Tablet, film coated Oral 15 MG - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9314464 No 2016-04-19 2031-07-04 US US9850229 No 2017-12-26 2030-08-27 US US10005761 No 2018-06-26 2030-08-27 US US9593100 No 2017-03-14 2030-08-27 US US9980944 No 2018-05-29 2033-10-18 US US9598376 No 2017-03-21 2033-10-18 US US8193229 No 2012-06-05 2023-03-13 US US8513293 No 2013-08-20 2023-03-13 US US7777050 No 2010-08-17 2023-03-13 US US8178693 No 2012-05-15 2023-03-13 US US9562016 No 2017-02-07 2033-10-18 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0499 mg/mL ALOGPS logP 3 ALOGPS logP 3.81 Chemaxon logS -4 ALOGPS pKa (Strongest Acidic) 10.26 Chemaxon pKa (Strongest Basic) 5.3 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 88.41 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 98.02 m3·mol-1 Chemaxon Polarizability 38.55 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0000900000-611f9ca261be4b64ea83 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-01dr-0009800000-49b4276f279db04bc60b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-014l-0009400000-c0ead1fc64a3cdaebd2d Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-5009300000-944283b5294b7bcd2110 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-06ri-0049100000-04fe4b0a75a92e3ebe86 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-9000000000-308ba3122a7cc4b1a574 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 184.66072 predictedDeepCCS 1.0 (2019) [M+H]+ 187.01872 predictedDeepCCS 1.0 (2019) [M+Na]+ 194.30202 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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). Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126)
- Specific Function
- Atp binding
- Gene Name
- MAP2K2
- Uniprot ID
- P36507
- Uniprot Name
- Dual specificity mitogen-activated protein kinase kinase 2
- Molecular Weight
- 44423.735 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis
- Specific Function
- Atp binding
- Gene Name
- MAP2K1
- Uniprot ID
- Q02750
- Uniprot Name
- Dual specificity mitogen-activated protein kinase kinase 1
- Molecular Weight
- 43438.65 Da
References
- FDA Approved Drug Products: MEKTOVI® (binimetinib) tablets, for oral use [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808, PubMed:24525562). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558)
- Specific Function
- Enzyme binding
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1A1
- Molecular Weight
- 59590.91 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- Aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (r)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- FDA Approved Drug Products: MEKTOVI® (binimetinib) tablets, for oral use [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- Antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Cavalieri G, Cilurzo G, Pettorosso L, Mansueto A, Laurini E, Pricl S: Biophysical and docking study on the interaction of anticancer drugs encorafenib and binimetinib with human serum albumin. Eur J Pharm Sci. 2023 Oct 1;189:106550. doi: 10.1016/j.ejps.2023.106550. Epub 2023 Jul 30. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- Abc-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- FDA Approved Drug Products: MEKTOVI® (binimetinib) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- Abc-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- FDA Approved Drug Products: MEKTOVI® (binimetinib) tablets, for oral use [Link]
Drug created at October 20, 2016 21:06 / Updated at November 24, 2023 04:34