Details of the Drug

General Information of Drug (ID: DM2JGQ3)

Drug Name
Trametinib
Synonyms
GSK 1120212; GSK-1120212; GSK1120212; JTP 74057; JTP-74057; Mekinist; Trametinib (GSK1120212); Trametinib (GSK1120212JTP 74057); Trametinib (MEK inhibitor); 33E86K87QN; A1-01871; AK174783; CHEBI:75998; UNII-33E86K87QN
Indication
Disease Entry ICD 11 Status REF
Melanoma 2C30 Approved [1]
Metastatic melanoma 2E2Z Approved [2]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [3]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [3]
Affected Organisms
Humans and other mammals
ATC Code
L01EE01: Trametinib
L01EE: Mitogen-activated protein kinase (MEK) inhibitors
L01E: PROTEIN KINASE INHIBITORS
L01: ANTINEOPLASTIC AGENTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 615.4
Logarithm of the Partition Coefficient (xlogp) 3.4
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 6
ADMET Property
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 22.2 mcg/L []
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 1.5 h []
Bioavailability
The bioavailability of drug is 72% []
Clearance
The apparent clearance of drug is 4.9 L/h []
Elimination
80% of the dose is excreted in the feces, and less than 20% of the dose is excreted in the urine with <0.1% of the excreted dose in the form of the parent compound []
Half-life
The concentration or amount of drug in body reduced by one-half in 3.9 - 4.8 days []
Metabolism
The drug is metabolized via the deacetylation alone or with mono-oxygenation or in combination with glucuronidation biotransformation pathways in vitro []
Vd
The volume of distribution (Vd) of drug is 214 L []
Chemical Identifiers
Formula
C26H23FIN5O4
IUPAC Name
N-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide
Canonical SMILES
CC1=C2C(=C(N(C1=O)C)NC3=C(C=C(C=C3)I)F)C(=O)N(C(=O)N2C4=CC=CC(=C4)NC(=O)C)C5CC5
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)
InChIKey
LIRYPHYGHXZJBZ-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
11707110
ChEBI ID
CHEMBL2103875
CAS Number
871700-17-3
UNII
33E86K87QN
DrugBank ID
DB08911
TTD ID
D04XVN
ACDINA ID
D00694
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
MAPK/ERK kinase kinase (MAP3K) TTROQ37 NOUNIPROTAC Modulator [4]
HUMAN ERK activator kinase 1 (MEK1) TTAW3TO MP2K1_HUMAN Inhibitor [3]
HUMAN ERK activator kinase 2 (MEK2) TTWX403 MP2K2_HUMAN Inhibitor [3]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Gene/Protein Processing [5]
Guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) OTOODWTU GNAQ_HUMAN Drug Response [5]
Guanine nucleotide-binding protein subunit alpha-11 (GNA11) OT0K99TO GNA11_HUMAN Drug Response [5]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Post-Translational Modifications [5]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Post-Translational Modifications [5]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Gene/Protein Processing [5]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Post-Translational Modifications [5]
Tumor necrosis factor receptor superfamily member 16 (NGFR) OTPKSM49 TNR16_HUMAN Gene/Protein Processing [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Trametinib (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Gilteritinib DMTI0ZO Moderate Decreased clearance of Trametinib due to the transporter inhibition by Gilteritinib. Acute myeloid leukaemia [2A60] [7]
Erdafitinib DMI782S Moderate Decreased clearance of Trametinib due to the transporter inhibition by Erdafitinib. Bladder cancer [2C94] [8]
Tucatinib DMBESUA Moderate Decreased clearance of Trametinib due to the transporter inhibition by Tucatinib. Breast cancer [2C60-2C6Y] [9]
Lasmiditan DMXLVDT Moderate Decreased clearance of Trametinib due to the transporter inhibition by Lasmiditan. Migraine [8A80] [10]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Mannitol E00103 6251 Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Sodium lauryl sulfate E00464 3423265 Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Carmellose sodium E00625 Not Available Disintegrant
Eisenoxyd E00585 56841934 Colorant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Hypromellose E00634 Not Available Coating agent
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 4000 E00654 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polysorbate 80 E00665 Not Available Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Haematite red E00236 14833 Colorant
Hydrophobic colloidal silica E00285 24261 Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline E00698 Not Available Adsorbent; Suspending agent; Diluent
⏷ Show the Full List of 14 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Trametinib 2 mg tablet 2 mg Oral Tablet Oral
Trametinib 0.5 mg tablet 0.5 mg Oral Tablet Oral
Trametinib 1 mg tablet 1 mg Oral Tablet Oral
Trametinib Dimethyl Sulfoxide eq 2mg tablet eq 2mg Tablet Oral
Trametinib Dimethyl Sulfoxide eq 0.5mg tablet eq 0.5mg Tablet Oral
Trametinib Dimethyl Sulfoxide eq 1mg tablet eq 1mg Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6495).
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
4 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
5 Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
6 Harnessing autophagy to overcome mitogen-activated protein kinase kinase inhibitor-induced resistance in metastatic melanoma. Br J Dermatol. 2019 Feb;180(2):346-356. doi: 10.1111/bjd.17333. Epub 2018 Nov 25.
7 Cerner Multum, Inc. "Australian Product Information.".
8 Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
9 Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
10 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.