U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C17H15BrClFN4O3
Molecular Weight 457.6815
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SELUMETINIB

SMILES

Cn1cnc2c1cc(c(c2F)Nc3ccc(cc3Cl)Br)C(=NOCCO)O

InChI

InChIKey=CYOHGALHFOKKQC-UHFFFAOYSA-N
InChI=1S/C17H15BrClFN4O3/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)

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17332304

Selumetinib (AZD6244 or ARRY-142886) is a potent, selective, and ATP-uncompetitive inhibitor of Ras-Raf-mitogen-activated protein kinase kinase (MEK1/2). This inhibition can prevent ERK activation, disrupt downstream signal transduction, and inhibit cancer cell proliferation and survival. Selumetinib has shown tumour suppressive activity in multiple rodent models of human cancer including melanoma, pancreatic, colon, lung, and breast cancers. AstraZeneca is responsible for development and commercialization of selumetinib.

CNS Activity

CNS Active
3730
Curator's Comment:: I.p. injection of AZD6244 prevented the development of pain in rats subjected to the chronic constriction injury and reversed already established pain in the spared nerve injury model. No human data available.

Originator

Approval Year

2020
833
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
7728
 14.0 nM [IC50]
Inhibitor
7728
 14.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
643
Unknown

Approved Use

Unknown
Primary
Phase III
643
Unknown

Approved Use

Unknown
Primary
Phase III
643
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
647 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/21519015
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SELUMETINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3299 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/21519015
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SELUMETINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/21519015
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SELUMETINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.4%
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412920/
SELUMETINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
Disc. AE: Creatinine increased, Weight increased...
AEs leading to
discontinuation/dose reduction:
Creatinine increased (2%)
Weight increased (2%)
Diarrhea (2%)
Paronychia (2%)
Malignant peripheral nerve sheath tumor (2%)
Acute kidney injury (2%)
Skin ulcer (2%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
Disc. AE: Vomiting, Paronychia...
AEs leading to
discontinuation/dose reduction:
Vomiting (>5)
Paronychia (>5)
Diarrhea (>5)
Nausea (>5)
Abdominal pain (>5)
Rash (>5)
Skin infection (>5)
Influenza like illness (>5)
Pyrexia (>5)
Weight gain (>5)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
100 mg 2 times / day steady, oral
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/20179232
unhealthy, 57.9 years (range: 30-76 years)
n = 8
Health Status: unhealthy
Age Group: 57.9 years (range: 30-76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/20179232
DLT: Acneiform dermatitis, Pleural effusion...
Dose limiting toxicities:
Acneiform dermatitis (grade 3)
Pleural effusion (grade 3)
Sources:
https://pubmed.ncbi.nlm.nih.gov/20179232
75 mg 2 times / day steady, oral
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/20179232
unhealthy, 57.9 years (range: 30-76 years)
n = 7
Health Status: unhealthy
Age Group: 57.9 years (range: 30-76 years)
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/20179232
DLT: Fatigue...
Dose limiting toxicities:
Fatigue (grade 3)
Sources:
https://pubmed.ncbi.nlm.nih.gov/20179232
300 mg 2 times / day steady, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
unhealthy, 58 years (range: 29–78 years)
n = 8
Health Status: unhealthy
Condition: Advanced Cancers
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
Other AEs: Dermatitis acneiform, Rash...
Other AEs:
Dermatitis acneiform (grade 3-4, 2 patients)
Rash (grade 3-4, 2 patients)
Rash erythematous (grade 3-4, 2 patients)
Rash maculo-papular (grade 3-4, 2 patients)
Rash pruritic (grade 3-4, 2 patients)
Diarrhea (grade 3-4, 1 patient)
Nausea (grade 1-2, 3 patients)
Fatigue (grade 1-2, 2 patients)
Peripheral edema (grade 1-2, 2 patients)
Vomiting (grade 1-2, 2 patients)
Blurred vision (grade 1-2, 3 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
AEs

AEs

AESignificanceDosePopulation
Acute kidney injury 2%
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
Creatinine increased 2%
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
Diarrhea 2%
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
Malignant peripheral nerve sheath tumor 2%
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
Paronychia 2%
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
Skin ulcer 2%
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
Weight increased 2%
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf
Abdominal pain >5
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
Diarrhea >5
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
Influenza like illness >5
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
Nausea >5
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
Paronychia >5
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
Pyrexia >5
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
Rash >5
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
Skin infection >5
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
Vomiting >5
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
Weight gain >5
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
Dose: 25 mg/m2, 2 times / day
Route: oral
Route: steady
Dose: 25 mg/m2, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
n = 50
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
Acneiform dermatitis grade 3
DLT
100 mg 2 times / day steady, oral
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/20179232
unhealthy, 57.9 years (range: 30-76 years)
n = 8
Health Status: unhealthy
Age Group: 57.9 years (range: 30-76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/20179232
Pleural effusion grade 3
DLT
100 mg 2 times / day steady, oral
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/20179232
unhealthy, 57.9 years (range: 30-76 years)
n = 8
Health Status: unhealthy
Age Group: 57.9 years (range: 30-76 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/20179232
Fatigue grade 3
DLT
75 mg 2 times / day steady, oral
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/20179232
unhealthy, 57.9 years (range: 30-76 years)
n = 7
Health Status: unhealthy
Age Group: 57.9 years (range: 30-76 years)
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/20179232
Fatigue grade 1-2, 2 patients
300 mg 2 times / day steady, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
unhealthy, 58 years (range: 29–78 years)
n = 8
Health Status: unhealthy
Condition: Advanced Cancers
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
Peripheral edema grade 1-2, 2 patients
300 mg 2 times / day steady, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
unhealthy, 58 years (range: 29–78 years)
n = 8
Health Status: unhealthy
Condition: Advanced Cancers
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
Vomiting grade 1-2, 2 patients
300 mg 2 times / day steady, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
unhealthy, 58 years (range: 29–78 years)
n = 8
Health Status: unhealthy
Condition: Advanced Cancers
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
Blurred vision grade 1-2, 3 patients
300 mg 2 times / day steady, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
unhealthy, 58 years (range: 29–78 years)
n = 8
Health Status: unhealthy
Condition: Advanced Cancers
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
Nausea grade 1-2, 3 patients
300 mg 2 times / day steady, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
unhealthy, 58 years (range: 29–78 years)
n = 8
Health Status: unhealthy
Condition: Advanced Cancers
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
Diarrhea grade 3-4, 1 patient
300 mg 2 times / day steady, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
unhealthy, 58 years (range: 29–78 years)
n = 8
Health Status: unhealthy
Condition: Advanced Cancers
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
Dermatitis acneiform grade 3-4, 2 patients
300 mg 2 times / day steady, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
unhealthy, 58 years (range: 29–78 years)
n = 8
Health Status: unhealthy
Condition: Advanced Cancers
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
Rash erythematous grade 3-4, 2 patients
300 mg 2 times / day steady, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
unhealthy, 58 years (range: 29–78 years)
n = 8
Health Status: unhealthy
Condition: Advanced Cancers
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
Rash maculo-papular grade 3-4, 2 patients
300 mg 2 times / day steady, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
unhealthy, 58 years (range: 29–78 years)
n = 8
Health Status: unhealthy
Condition: Advanced Cancers
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
Rash pruritic grade 3-4, 2 patients
300 mg 2 times / day steady, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
unhealthy, 58 years (range: 29–78 years)
n = 8
Health Status: unhealthy
Condition: Advanced Cancers
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
Rash grade 3-4, 2 patients
300 mg 2 times / day steady, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
unhealthy, 58 years (range: 29–78 years)
n = 8
Health Status: unhealthy
Condition: Advanced Cancers
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/18390968
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inducer
707

inhibitor
1467

substrate
1601
inhibitor
1604

substrate
936
inhibitor
1702
inhibitor
1475

OverviewOther

Other InhibitorOther SubstrateOther Inducer
BCRP
643

CYP1A2
1383

CYP2A6
627

CYP2B6
717

CYP2C19
1325

CYP2C8
818

CYP2E1
790

P-gp
1330

UGT1A1
192

UGT2B7
141

OATP1B1
733

OATP1B3
657

OCT1
480

OCT2
594

MATE1
290

MATE2
251
BCRP
515

CYP1A2
972

CYP2C19
910

CYP2E1
606

P-gp
1400

UGT1A1
393

UGT1A3
397
CYP1A2
637

CYP2B6
501

MATE1
5

MATE2
4

OAT1
25

OATP1B1
26

OATP1B3
6

OCT2
5
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2A6
659
 no
CYP2E1
871
 no
MATE1
292
 no
MATE2
251
 no
OCT1
495
 no
OCT2
595
 no
CYP2D6
1738
 weak [IC50 45.3 uM]
CYP2C8
865
 weak [IC50 52.1 uM]
UGT1A1
240
 weak [IC50 >100 uM]
UGT2B7
152
 weak [IC50 >100 uM]
CYP1A2
1532
 weak [IC50 >70 uM]
CYP2B6
884
 weak [IC50 >70 uM]
CYP2C19
1392
 weak [IC50 >70 uM]
CYP2C9
1648
 weak [IC50 >70 uM]
CYP3A4
1772
 weak [IC50 >70 uM]
BCRP
713
 weak
CYP1A2
1532
 weak
CYP2B6
884
 weak
CYP3A4
1772
 weak
MATE1
292
 weak
MATE2
251
 weak
OAT1
558
 weak
OATP1B1
748
 weak
OATP1B3
666
 weak
OCT2
595
 weak
P-gp
1514
 weak
OATP1B3
666
 yes [IC50 19 uM]
OATP1B1
748
 yes [IC50 8.76 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
BCRP
515
 weak
CYP1A2
972
 weak
CYP2C9
936
 weak
CYP2E1
606
 weak
P-gp
1400
 weak
UGT1A1
393
 yes
UGT1A3
397
 yes
CYP2C19
910
 yes
yes (co-administration study)
Comment: fluconazole increased selumetinib AUC by 53%
Page: 101, 107
CYP3A4
1601
 yes
yes (co-administration study)
Comment: itraconazole increased selumetinib AUC by 49%; fluconazole increased selumetinib exposure 50%; rifampicin reduced selumetinib exposure 51%; erythromycin increased selumetinib AUC by 40%; efavirenz reduced selumetinib AUC by 40%
Page: 92, 101, 106
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1507
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:90227
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:90227
ChemicalBook
CB81871940
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB81871940
MolPort
MolPort-009-679-426
https://www.molport.com/shop/molecule-link/MolPort-009-679-426
Selleck Chemicals
AZD6244
http://www.selleckchem.com/products/AZD6244.html
ZINC
ZINC000031773258
http://zinc15.docking.org/substances/ZINC000031773258
eMolecules
31507604
https://www.emolecules.com/cgi-bin/more?vid=31507604
PubMed

PubMed

TitleDatePubMed
Mutations of the BRAF gene in human cancer.
2002 Jun 27
Targeted inhibition of the extracellular signal-regulated kinase kinase pathway with AZD6244 (ARRY-142886) in the treatment of hepatocellular carcinoma.
2007 Jan
Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor.
2007 Mar 1
AZD6244 and doxorubicin induce growth suppression and apoptosis in mouse models of hepatocellular carcinoma.
2007 Sep
Blockade of MEK signaling potentiates 5-Aza-2'-deoxycytidine-induced apoptosis and upregulation of p21(waf1) in acute myelogenous leukemia cells.
2009 Sep 1
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
2010 Nov 24
Comprehensive analysis of kinase inhibitor selectivity.
2011 Oct 30
Exon capture analysis of G protein-coupled receptors identifies activating mutations in GRM3 in melanoma.
2011 Sep 25
The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition.
2012 Apr 10
Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification.
2012 Jul
Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by cAMP-dependent protein kinase A activation in human lung and colorectal cancer cells.
2012 May 8
MEK and the inhibitors: from bench to bedside.
2013 Apr 12
Flavanoids induce expression of the suppressor of cytokine signalling 3 (SOCS3) gene and suppress IL-6-activated signal transducer and activator of transcription 3 (STAT3) activation in vascular endothelial cells.
2013 Sep 1
Synergistic induction of human cathelicidin antimicrobial peptide gene expression by vitamin D and stilbenoids.
2014 Mar
Patents

Patents

07235537
3
07425637
3
07576114
3
JP2011506420A
5

Sample Use Guides

In Vivo Use Guide
Oral selumetinib (50, 100 and 200mg bid for 28-day cycles) was well tolerated in patients with refractory solid tumours. The maximum tolerated dose was established to be 200mg bid. 100 mg dose of selumetinib proved to be more tolerable than the 200mg dose over prolonged periods. The 100mg dose has been chosen for phase II studies.
Route of Administration: Oral
In Vitro Use Guide
The sensitivity of a large panel of cell lines to Selumetinib (AZD6244 or ARRY-142886) was evaluated in vitro and correlated with RAS and BRAF gene mutation status. There was a wide range of sensitivity to AZD6244 from highly sensitive (IC50, <100 nmol/L) to highly resistant (>10 μmol/L)
Name Type Language
SELUMETINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
5-((4-BROMO-2-CHLOROPHENYL)AMINO)-4-FLUORO-N-(2-HYDROXYETHOXY)-1-METHYL-1H-BENZIMIDAZOLE-6-CARBOXAMIDE
Systematic Name English
ARRY-886
Code English
AZD6244
Code English
SELUMETINIB [INN]
Common Name English
AZD-6244
Code English
1H-BENZIMIDAZOLE-6-CARBOXAMIDE, 5-((4-BROMO-2-CHLOROPHENYL)AMINO)-4-FLUORO-N-(2- HYDROXYETHOXY)-1-METHYL-
Common Name English
SELUMETINIB [WHO-DD]
Common Name English
SELUMETINIB [USAN]
Common Name English
Classification Tree Code System Code
EU-Orphan Drug EU/3/18/2050
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
FDA ORPHAN DRUG 624017
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
FDA ORPHAN DRUG 475815
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
NCI_THESAURUS C69145
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
FDA ORPHAN DRUG 471015
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
Code System Code Type Description
RXCUI
2289380
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
PRIMARY
INN
9078
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
PRIMARY
EPA CompTox
606143-52-6
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
PRIMARY
CAS
606143-52-6
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
PRIMARY
DRUG CENTRAL
5388
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
PRIMARY
NCI_THESAURUS
C66939
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
PRIMARY
WIKIPEDIA
SELUMETINIB
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
PRIMARY
FDA UNII
6UH91I579U
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
PRIMARY
PUBCHEM
10127622
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
PRIMARY
DRUG BANK
DB11689
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
PRIMARY
ChEMBL
CHEMBL1614701
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
PRIMARY
EVMPD
SUB32237
Created by admin on Sat Jun 26 14:35:45 UTC 2021 , Edited by admin on Sat Jun 26 14:35:45 UTC 2021
PRIMARY
ACTIVE MOIETY
Structure of SELUMETINIB
METABOLITE (PARENT)
Structure of AZ-12791138
METABOLITE (PARENT)
Structure of AZ-133266637
METABOLITE ACTIVE (PARENT)
Structure of N-DESMETHYL SELUMETINIB
SALT/SOLVATE (PARENT)
Structure of SELUMETINIB SULFATE
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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