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], [2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

615.4

Topological Polar Surface Area (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 [3]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1.5 h [3]
Bioavailability: The bioavailability of drug is 72% [3]
Clearance: The apparent clearance of drug is 4.9 L/h [4]
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 [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 3.9 - 4.8 days [3]
Metabolism: The drug is metabolized via the deacetylation alone or with mono-oxygenation or in combination with glucuronidation biotransformation pathways in vitro [3]
Vd: The volume of distribution (Vd) of drug is 214 L [4]

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: CHEBI:75998
CAS Number: 871700-17-3
DrugBank ID: DB08911
TTD ID: D04XVN
ACDINA ID: D00694

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	[2]

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Molecular Interaction Atlas (MIA)

MIA Detail

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	DMWQ4MZ	Moderate	Decreased clearance of Trametinib due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[13]
Erdafitinib	DMI782S	Moderate	Decreased clearance of Trametinib due to the transporter inhibition by Erdafitinib.	Bladder cancer [2C94]	[14]
Tucatinib	DMBESUA	Moderate	Decreased clearance of Trametinib due to the transporter inhibition by Tucatinib.	Breast cancer [2C60-2C6Y]	[15]
Lasmiditan	DMXLVDT	Moderate	Decreased clearance of Trametinib due to the transporter inhibition by Lasmiditan.	Migraine [8A80]	[16]
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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
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⏷ 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	Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
3	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
5	MEK and the inhibitors: from bench to bedside. J Hematol Oncol. 2013; 6: 27.
6	RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer.Cancer Res.2009 Sep 1;69(17):6839-47.
7	Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by cAMP-dependent protein kinase A activation in human lung and colorectal cancer cells.Br J Cancer.2012 May 8;106(10):1648-59.
8	Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells. Int J Cancer. 2013 Nov;133(9):2089-101.
9	The dual RAF/MEK inhibitor CH5126766/RO5126766 may be a potential therapy for RAS-mutated tumor cells.PLoS One.2014 Nov 25;9(11):e113217.
10	E6201, a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase-1: in vivo effects on cutaneous inflammatory responses by topical administration. J Pharmacol Exp Ther. 2010 Oct;335(1):23-31.
11	Clinical pipeline report, company report or official report of Roche.
12	doi: 10.1158/1535-7163.TARG-13-B281
13	Cerner Multum, Inc. "Australian Product Information.".
14	Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
15	Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
16	Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.