Drug Details

General Information of the Drug (ID: DR8750)
Name
Trametinib
Synonyms
Trametinib; 871700-17-3; GSK1120212; Mekinist; GSK-1120212; JTP 74057; JTP-74057; GSK 1120212; Trametinib (GSK1120212); N-[3-[3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl]acetamide; GSK212; UNII-33E86K87QN; TMT212; CHEBI:75998; TMT-212; 33E86K87QN; N-(3-{3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl}phenyl)acetamide; N-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide; Trametinib [USAN:INN]; trametinibum; JTP74057; N-(3-(3-Cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7- tetrahydropyrido(4,3-d)pyrimidin-1(2H)-yl)phenyl)acetamide; N-(3-{3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7- tetrahydropyrido(4,3-d)pyrimidin-1(2H)-yl}phenyl)acetamide; QOM; Trametinib (USAN); Trametinib (GSK1120212JTP 74057); cc-37; SCHEMBL170938; C26H23FIN5O4; GTPL6495; QCR-39; GSK1120212 (Trametinib); CHEMBL2103875; EX-A022; BCPP000218; DTXSID901007381; HMS3295I05; HMS3656J11; AOB87707; BCP02307; ABP000312; BDBM50531540; MFCD17215075; NSC758246; NSC800956; RW4149; s2673; ZINC43100709; AKOS015850628; AM90271; CCG-264976; CS-0060; DB08911; EX-5957; NSC-758246; NSC-800956; SB16553; NCGC00263180-01; NCGC00263180-07; NCGC00263180-14; AC-25891; AK174783; AS-19382; HY-10999; N-[3-[3-cyclopropyl-5-(2-fluoro-4-iodo-anilino)-6,8-dimethyl-2,4,7-trioxo-pyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide; AB0008115; FT-0688438; SW218089-2; X7454; A11029; A25168; D10175; GSK1120212 - JTP-74057; S-7800; GSK-1120212/GSK1120212/; GSK1120212,JTP-74057, GSK212; SR-01000941589; A1-01871; J-523325; Q7833138; SR-01000941589-1; BRD-K12343256-001-01-4; Acetamide, N-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-3,4,6,7-tetrahydro-6,8- dimethyl-2,4,7-trioxopyrido(4,3-d)pyrimidin-1(2H)-yl)phenyl)-; Acetamide, N-[3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl]-; N-(3-(3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)acetamide; N-[3-[3-Cyclopropyl-5-[(2-Fluoro-4-Iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2h)-yl]phe nyl]acetamide; N-[3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxopyrido[3,4-e]pyrimidin-1-yl]phenyl]acetamide; N-{3-[3-Cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl}ethanimidic acid; N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide
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Molecular Type
Small molecule
Disease Melanoma [ICD-11: 2C30] Approved [1]
Structure
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2D MOL

3D MOL

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
Clearance
The drug present in the plasma can be removed from the body at the rate of 0.8 mL/min/kg
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
Half-life
The concentration or amount of drug in body reduced by one-half in 229 hours
Metabolism
The drug is metabolized via the deacetylation alone or with mono-oxygenation or in combination with glucuronidation biotransformation pathways in vitro
Unbound Fraction
The unbound fraction of drug in plasma is 0.03%
Vd
The volume of distribution (Vd) of drug is 214 L
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 13.94 L/kg
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Formula
C26H23FIN5O4
PubChem CID
11707110
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
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
CAS Number
CAS 871700-17-3
ChEBI ID
CHEBI:75998
TTD Drug ID
D04XVN
DrugBank ID
DB08911
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Metformin      Galega officinalis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression PIK3CB  Molecule Info 
Pathway MAP
                    In-vitro Model D04 CVCL_H604 Melanoma Homo sapiens
MM415 CVCL_2608 Melanoma Homo sapiens
MM485 CVCL_2610 Melanoma Homo sapiens
SK-MEL-2 CVCL_0069 Melanoma Homo sapiens
MaMel30I CVCL_A165 Melanoma Homo sapiens
MaMel27II CVCL_A163 Melanoma Homo sapiens
                    Experimental
                    Result(s)		 Metformin and trametinib combinations are effective in preclinical models and may be a possible option for treatment of NRAS mutant cancers.
Target and Pathway
Target(s) MAPK/ERK kinase kinase (MAP3K)  Molecule Info  [3]
KEGG Pathway MAPK signaling pathway Click to Show/Hide
2 ErbB signaling pathway
3 Ras signaling pathway
4 Rap1 signaling pathway
5 cGMP-PKG signaling pathway
6 cAMP signaling pathway
7 Chemokine signaling pathway
8 HIF-1 signaling pathway
9 FoxO signaling pathway
10 Sphingolipid signaling pathway
11 Oocyte meiosis
12 PI3K-Akt signaling pathway
13 Vascular smooth muscle contraction
14 Dorso-ventral axis formation
15 VEGF signaling pathway
16 Osteoclast differentiation
17 Focal adhesion
18 Gap junction
19 Signaling pathways regulating pluripotency of stem cells
20 Toll-like receptor signaling pathway
21 Natural killer cell mediated cytotoxicity
22 T cell receptor signaling pathway
23 B cell receptor signaling pathway
24 Fc epsilon RI signaling pathway
25 Fc gamma R-mediated phagocytosis
26 TNF signaling pathway
27 Long-term potentiation
28 Neurotrophin signaling pathway
29 Cholinergic synapse
30 Serotonergic synapse
31 Long-term depression
32 Regulation of actin cytoskeleton
33 Insulin signaling pathway
34 GnRH signaling pathway
35 Progesterone-mediated oocyte maturation
36 Estrogen signaling pathway
37 Melanogenesis
38 Prolactin signaling pathway
39 Thyroid hormone signaling pathway
40 Oxytocin signaling pathway
41 Prion diseases
42 Alcoholism
43 Hepatitis B
44 Influenza A
45 Pathways in cancer
46 Proteoglycans in cancer
47 MicroRNAs in cancer
48 Colorectal cancer
49 Renal cell carcinoma
50 Pancreatic cancer
51 Endometrial cancer
52 Glioma
53 Prostate cancer
54 Thyroid cancer
55 Melanoma
56 Bladder cancer
57 Chronic myeloid leukemia
58 Acute myeloid leukemia
59 Non-small cell lung cancer
60 Central carbon metabolism in cancer
61 Choline metabolism in cancer
Pathwhiz Pathway Fc Epsilon Receptor I Signaling in Mast Cells Click to Show/Hide
2 Insulin Signalling
Reactome MAPK3 (ERK1) activation Click to Show/Hide
2 Uptake and function of anthrax toxins
3 RAF activation
4 MAP2K and MAPK activation
5 Negative feedback regulation of MAPK pathway
6 MAP3K8 (TPL2)-dependent MAPK1/3 activation
WikiPathways Toll-like receptor signaling pathway Click to Show/Hide
2 Serotonin Receptor 4/6/7 and NR3C Signaling
3 Serotonin Receptor 2 and ELK-SRF/GATA4 signaling
4 Serotonin HTR1 Group and FOS Pathway
5 TCR Signaling Pathway
6 ErbB Signaling Pathway
7 Hypothetical Network for Drug Addiction
8 Senescence and Autophagy in Cancer
9 EPO Receptor Signaling
10 Regulation of Actin Cytoskeleton
11 IL-2 Signaling Pathway
12 Insulin Signaling
13 EGF/EGFR Signaling Pathway
14 MAPK Cascade
15 MAPK Signaling Pathway
16 TGF beta Signaling Pathway
17 IL-6 signaling pathway
18 Signaling of Hepatocyte Growth Factor Receptor
19 Kit receptor signaling pathway
20 IL-3 Signaling Pathway
21 Bladder Cancer
22 Cardiac Hypertrophic Response
23 MAP kinase activation in TLR cascade
24 RAF/MAP kinase cascade
25 Nanoparticle-mediated activation of receptor signaling
26 Structural Pathway of Interleukin 1 (IL-1)
27 Genes and (Common) Pathways Underlying Drug Addiction
28 Nifedipine Activity
29 PDGF Pathway
30 BDNF signaling pathway
31 Integrated Pancreatic Cancer Pathway
32 Oncostatin M Signaling Pathway
33 Corticotropin-releasing hormone
34 Interleukin-11 Signaling Pathway
35 AGE/RAGE pathway
36 B Cell Receptor Signaling Pathway
37 Prostate Cancer
38 Signaling Pathways in Glioblastoma
39 TSLP Signaling Pathway
40 IL-9 Signaling Pathway
41 Endothelin Pathways
42 IL-7 Signaling Pathway
43 Leptin signaling pathway
44 RANKL/RANK Signaling Pathway
45 IL-1 signaling pathway
46 Signaling by FGFR
47 Integrin-mediated Cell Adhesion
48 L1CAM interactions
49 MicroRNAs in cardiomyocyte hypertrophy
50 Regulation of toll-like receptor signaling pathway
51 Osteopontin Signaling
52 IL-5 Signaling Pathway
References
Reference 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).
Reference 2 Metformin and trametinib have synergistic effects on cell viability and tumor growth in NRAS mutant cancer. Oncotarget. 2015 Jan 20;6(2):969-78.
Reference 3 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
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