Trametinib

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H23FIN5O4
Molecular Weight	615.3948
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C(=O)C(C)=C2N(C(=O)N(C3CC3)C(=O)C2=C1NC4=C(F)C=C(I)C=C4)C5=CC(NC(C)=O)=CC=C5

InChI

InChIKey=LIRYPHYGHXZJBZ-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C26H23FIN5O4
Molecular Weight	615.3948
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204114s001lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/?term=24875464; http://www.ncbi.nlm.nih.gov/pubmed/23846731

Trametinib is a reversible and specific inhibitor of mitogen-activated protein kinase kinases MEK1 and MEK2 which are involved in a RAS/RAF/MEK/ERK signaling pathway and control cell growth, survival, and differentiation. By inhibiting MEK1 and MEK2 trametinib blocks dual phosphorylation of ERK1/2 and stops cell cycling. In addition, trametinib blocks BRAF pathway in the cells with BRAF V600E mutations. Trametinib (as a single agent and in combination with dabrafenib) is approved for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dual specificity mitogen-activated protein kinase kinase 1 20 Target ID: Q02750 Gene ID: 5604.0 Gene Symbol: MAP2K1 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747351/	Antagonist 2849		0.9 nM [IC50]
Dual specificity mitogen-activated protein kinase kinase 2 10 Target ID: P36507 Gene ID: 5605.0 Gene Symbol: MAP2K2 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747351/	Antagonist 2849		1.8 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Melanoma 88 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204114s001lbl.pdf	Primary		Approved 8583	MEKINIST Approved Use Indicated, as a single agent or in combination with dabrafenib, for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations Launch Date 2013

C_max

Value	Dose	Analyte	Population
22 ng/mL OTHER GOV'T https://www.ema.europa.eu/en/documents/product-information/mekinist-epar-product-information_en.pdf	2 mg 1 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TRAMETINIB plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
9.5 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23893461	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	TRAMETINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8.03 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24606567	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	TRAMETINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
370 ng × h/mL OTHER GOV'T https://www.ema.europa.eu/en/documents/product-information/mekinist-epar-product-information_en.pdf	2 mg 1 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TRAMETINIB plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
498 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23893461	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	TRAMETINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
525 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24606567	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	TRAMETINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
127 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23893461	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		TRAMETINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
264 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24606567	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		TRAMETINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24606567	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		TRAMETINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
2 mg 2 times / day multiple, oral Dose: 2 mg, 2 times / day Route: oral Route: multiple Dose: 2 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000MedR.pdf	unhealthy, median age 54.5 years Health Status: unhealthy Age Group: median age 54.5 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000MedR.pdf	Disc. AE: Left ventricular dysfunction, Cardiac failure... AEs leading to discontinuation/dose reduction: Left ventricular dysfunction (0.9%) Cardiac failure (0.5%) Myocardial infarction (0.5%) Tachycardia (0.5%) ALT increased (0.5%) Bilirubin increased (0.5%) GGT increased (0.5%) CPK increased (0.5%) Pneumonitis (0.9%) Renal failure (0.9%) Rash (0.9%) Erythema nodosum (0.5%) Chorioretinopathy (0.5%) Retinal detachment (0.5%) Hepatic failure (0.5%) Hepatitis (0.5%) Hepatobiliary disease (0.5%) Duodenal perforation (0.5%) Esophagitis (0.5%) Vomiting (0.5%) Diarrhea (0.5%) Abdominal pain upper (0.5%) Face edema (0.5%) Edema peripheral (0.5%) Fatigue (0.5%) Pyrexia (0.5%) Decreased appetite (0.5%) Hyponatremia (0.5%) Cell death (0.5%) Hypersensitivity (0.5%) Corneal graft rejection (0.5%) Anemia (0.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000MedR.pdf
2 mg 2 times / day multiple, oral Dose: 2 mg, 2 times / day Route: oral Route: multiple Dose: 2 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000MedR.pdf	unhealthy, median age 54.5 years Health Status: unhealthy Age Group: median age 54.5 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000MedR.pdf	Disc. AE: Rash, Diarrhea... Other AEs: Hypertension, Rash... AEs leading to discontinuation/dose reduction: Rash (4%) Diarrhea (2%) Peripheral edema (2%) Transaminases increased (1%) Cardiac disorder (1%) Cellulitis (1%) Nausea (1%) Pyrexia (1%) Rash (9%) Acne (0.9%) Dermatitis acneiform (0.9%) Pruritus (0.9%) Erythema (0.5%) Rash maculo-papular (0.5%) Rash papular (0.5%) Skin ulcer (0.5%) Toxic skin eruption (0.5%) ALT increased (3%) AST increased (0.9%) CPK increased (0.9%) Alkaline phosphatase increased (0.5%) Electrocardiogram abnormal (0.5%) Decreased hemoglobin (0.5%) Stomatitis (0.9%) Abdominal pain (0.5%) Anal ulcer (0.5%) Diarrhea (0.5%) Lip ulceration (0.5%) Oral pain (0.5%) Rash pustular (0.9%) Folliculitis (0.5%) Klebsiella infection (0.5%) Nail infection (0.5%) Pulpitis dental (0.5%) Fatigue (0.9%) Mucosal inflammation (0.9%) Pyrexia (0.5%) Rhabdomyolysis (0.9%) Neck pain (0.5%) Exertional dyspnea (0.5%) Interstitial lung disease (0.5%) Nasal ulcer (0.5%) Conduction disorder (0.5%) Left ventricular dysfunction (0.5%) Hypertension (0.9%) Central serous retinopathy (0.5%) Hypertriglyceridemia (0.5%) Rash (grade 3, 7%) Acne (grade 3, 0.5%) Pruritus (grade 3, 0.9%) Rash papular (grade 3, 0.5%) ALT increased (grade 3, 0.9%) CPK increased (grade 3, 0.5%) Decreased hemoglobin (grade 3, 0.5%) Stomatitis (grade 3, 0.5%) Abdominal pain (grade 3, 0.5%) Lip ulceration (grade 3, 0.5%) Oral pain (grade 3, 0.5%) Rash pustular (grade 3, 0.5%) Folliculitis (grade 3, 0.5%) Klebsiella infection (grade 3, 0.5%) Fatigue (grade 3, 0.9%) Mucosal inflammation (grade 3, 0.9%) Rhabdomyolysis (grade 3, 0.9%) Exertional dyspnea (grade 3, 0.5%) Interstitial lung disease (grade 3, 0.5%) Conduction disorder (grade 3, 0.5%) Hypertension (grade 3, 0.9%) Hypertriglyceridemia (grade 3, 0.5%) Other AEs: Hypertension (grade 3, 13%) Rash (grade 3, 8%) Fatigue (grade 3, 4%) Anemia (grade 3, 2%) Dehydration (grade 3, 1%) ALT increased (grade 3, 2%) Dyspnea (grade 3, 1%) Hypoalbuminemia (grade 3, 1%) Pruritus (grade 3, 2%) Vomiting (grade 3, 1%) CPK increased (grade 3, 1%) Cellulitis (grade 3, 1%) Infection (grade 3, 1%) Rash (grade 4, 0.5%) Dehydration (grade 4, 0.5%) Dyspnea (grade 4, 0.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000MedR.pdf
2 mg 1 times / day multiple, oral Recommended Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22663011/	unhealthy, median age 55 years Health Status: unhealthy Age Group: median age 55 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22663011/	Other AEs: Skin rash, Skin rash... Other AEs: Skin rash (grade 3, 7.1%) Skin rash (grade 4, 0.5%) Fatigue (grade 3, 4%) Peripheral edema (grade 3, 1%) Acneiform dermatitis (grade 3, 1%) Nausea (grade 3, 1%) Alopecia (grade 3, <1%) Hypertension (grade 3, 12%) Vomiting (grade 3, 1%) Sources: https://pubmed.ncbi.nlm.nih.gov/22663011/
2 mg 1 times / day multiple, oral Recommended Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204114Orig1s000SumR.pdf https://pubmed.ncbi.nlm.nih.gov/22663011/	unhealthy, median age 55 years Health Status: unhealthy Age Group: median age 55 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204114Orig1s000SumR.pdf https://pubmed.ncbi.nlm.nih.gov/22663011/	Other AEs: Detachment of retinal pigment epithelium, Retinal vein occlusion... Other AEs: Detachment of retinal pigment epithelium (0.5%) Retinal vein occlusion (0.6%) Interstitial lung disease (2.4%) Skin rash (6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204114Orig1s000SumR.pdf https://pubmed.ncbi.nlm.nih.gov/22663011/
2 mg 1 times / day multiple, oral Recommended Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204114Orig1s000SumR.pdf	unhealthy, median age 55 years Health Status: unhealthy Age Group: median age 55 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204114Orig1s000SumR.pdf	Other AEs: Cardiomyopathy... Other AEs: Cardiomyopathy (7%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204114Orig1s000SumR.pdf
10 mg 1 times / day multiple, oral Highest studied dose Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22805291/	unhealthy, median age 58.5 years Health Status: unhealthy Age Group: median age 58.5 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22805291/	DLT: Central serous retinopathy, Diarrhoea... Dose limiting toxicities: Central serous retinopathy (grade 2) Diarrhoea (grade 3) Rash (grade 3) Sources: https://pubmed.ncbi.nlm.nih.gov/22805291/
10 mg 1 times / day multiple, oral Highest studied dose Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204114s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/22805291/	unhealthy, median age 58.5 years Health Status: unhealthy Age Group: median age 58.5 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204114s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/22805291/	Other AEs: Detachment of retinal pigment epithelium... Other AEs: Detachment of retinal pigment epithelium (28%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204114s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/22805291/
4 mg 1 times / day multiple, oral Highest studied dose Dose: 4 mg, 1 times / day Route: oral Route: multiple Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22805291/	unhealthy, median age 58.5 years Health Status: unhealthy Age Group: median age 58.5 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22805291/	DLT: Central serous retinopathy... Dose limiting toxicities: Central serous retinopathy (grade 2) Sources: https://pubmed.ncbi.nlm.nih.gov/22805291/
4 mg 1 times / day multiple, oral Highest studied dose Dose: 4 mg, 1 times / day Route: oral Route: multiple Dose: 4 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204114s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/22805291/	unhealthy, median age 58.5 years Health Status: unhealthy Age Group: median age 58.5 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204114s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/22805291/	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204114s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/22805291/
3 mg 1 times / day multiple, oral MTD Dose: 3 mg, 1 times / day Route: oral Route: multiple Dose: 3 mg, 1 times / day Sources: https://www.ema.europa.eu/en/documents/assessment-report/mekinist-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/22805291/	unhealthy, median age 58.5 years Health Status: unhealthy Age Group: median age 58.5 years Sex: M+F Sources: https://www.ema.europa.eu/en/documents/assessment-report/mekinist-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/22805291/	Disc. AE: Fatigue... AEs leading to discontinuation/dose reduction: Fatigue (8.3%) Sources: https://www.ema.europa.eu/en/documents/assessment-report/mekinist-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/22805291/
2 mg 1 times / day multiple, oral Recommended Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22805291/	unhealthy, median age 58.5 years Health Status: unhealthy Age Group: median age 58.5 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22805291/	Other AEs: Acneiform dermatitis, Diarrhoea... Other AEs: Acneiform dermatitis (grade 1, 49%) Diarrhoea (grade 1, 34%) Fatigue (grade 1, 19%) Peripheral oedema (grade 1, 26%) Nausea (grade 1, 20%) Vomiting (grade 1, 7%) Pruritus (grade 1, 14%) Fissures of skin (grade 1, 16%) Decreased appetite (grade 1, 9%) Eye disorders NEC (grade 1, 9%) Mucosal inflammation (grade 1, 4%) Constipation (grade 1, 3%) Left ventricular ejection fraction decreased (grade 1, 3%) Periorbital oedema (grade 1, 7%) Thrombocytopenia (grade 1, 1%) Dry mouth (grade 1, 3%) Acneiform dermatitis (grade 2, 31%) Diarrhoea (grade 2, 10%) Fatigue (grade 2, 10%) Peripheral oedema (grade 2, 3%) Nausea (grade 2, 6%) Vomiting (grade 2, 4%) Pruritus (grade 2, 6%) Fissures of skin (grade 2, 6%) Decreased appetite (grade 2, 1%) Constipation (grade 2, 1%) Left ventricular ejection fraction decreased (grade 2, 6%) Acneiform dermatitis (grade 3, 4%) Diarrhoea (grade 3, 1%) Fatigue (grade 3, 1%) Vomiting (grade 3, 1%) Eye disorders NEC (grade 3, 1%) Left ventricular ejection fraction decreased (grade 3, 1%) Sources: https://pubmed.ncbi.nlm.nih.gov/22805291/
2 mg 1 times / day multiple, oral Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22805291/	unhealthy, median age 58.5 years Health Status: unhealthy Age Group: median age 58.5 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22805291/	DLT: Rash... Dose limiting toxicities: Rash (grade 3) Sources: https://pubmed.ncbi.nlm.nih.gov/22805291/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 substrate 1946 inhibitor 2252	substrate 1193 inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1057 P-gp 1741 BCRP 910 OATP1B1 1079 OATP1B3 961 CYP1A2 2153 CYP2A6 879 CYP2B6 926 CYP2C19 2057	CYP1A2 1197 CYP2C8 810 CYP2C19 1119 P-gp 2052 BCRP 697

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=8 Page: -	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=8 Page: -	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=8 Page: -	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=8 Page: -	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=8 Page: -	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=8 Page: -	yes [EC50 2.7 uM]	no (co-administration study) Comment: Based on cross-study comparisons, oral administration of trametinib 2 mg QD with everolimus (sensitive CYP3A4 substrate) 5 mg QD had no clinically important effect on the exposure (AUC and Cmax) of everolimus. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=8 Page: -
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=8 Page: -	yes [IC50 0.34 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=31 Page: -	yes [IC50 0.94 uM]
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=31 Page: -	yes [IC50 1.1 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=31 Page: -	yes [IC50 1.3 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=8 Page: -	yes [IC50 4.1 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=8 Page: -	yes [IC50 5 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=31 Page: -	yes [IC50 5.5 uM]

Drug as victim

Target	Modality	Activity
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=30 Page: -	no
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=19 Page: -	no
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=19 Page: -	no
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=19 Page: -	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=19 Page: -	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=19 Page: -	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=30 Page: -	no
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000ClinPharmR.pdf#page=19 Page: -	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204114Orig1s000PharmR.pdf#page=14 Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:75998	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:75998
ChemicalBook	CB32514557	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB32514557
eMolecules	36723803	https://www.emolecules.com/cgi-bin/more?vid=36723803
MolPort	MolPort-019-879-136	https://www.molport.com/shop/molecule-link/MolPort-019-879-136
Selleck Chemicals	gsk1120212-(jtp-74057)	http://www.selleckchem.com/products/gsk1120212-(jtp-74057).html
ZINC	ZINC000043100709	http://zinc15.docking.org/substances/ZINC000043100709

PubMed

Title	Date	PubMed
MEK and the inhibitors: from bench to bedside.	2013-04-12	23587417
Trametinib (GSK1120212) in the treatment of melanoma.	2013-04	23432625
Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner.	2012-08-15	22733540
Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo.	2011-07	21523318
GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition.	2011-03-01	21245089

Patents

Sample Use Guides

In Vivo Use Guide

Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with MEKINIST. The recommended dosage regimens of MEKINIST are 2 mg orally once daily as a single agent or in combination with dabrafenib 150 mg orally twice daily.Take MEKINIST at least 1 hour before or at least 2 hours after a meal.

Route of Administration: Oral

In Vitro Use Guide

A375 and SK-MEL-28 untransfected or transfected with Mcl-1 plasmid were treated with 2 nM trametinib for 72 hours. The cell survival was evaluated by sulforhodamine B assay.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 20:13:14 GMT 2025` Edited by `admin` on `Mon Mar 31 20:13:14 GMT 2025`
Record UNII	33E86K87QN
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Trametinib

Official Name

English

JTP 74057

Preferred Name

English

Trametinib [MI]

Common Name

English

Trametinib [WHO-DD]

Common Name

English

JTP-74057

Code

English

TMT-212

Code

English

TMT212

Code

English

Trametinib [VANDF]

Common Name

English

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

Systematic Name

English

Trametinib [USAN]

Common Name

English

GSK1120212

Code

English

GSK-1120212

Code

English

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]-

Systematic Name

English

Trametinib [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C69145