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

Details

Stereochemistry ACHIRAL
Molecular Formula C17H15BrClFN4O3
Molecular Weight 457.681
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SELUMETINIB

SMILES

CN1C=NC2=C(F)C(NC3=CC=C(Br)C=C3Cl)=C(C=C12)C(=O)NOCCO

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
Molecular Formula C17H15BrClFN4O3
Molecular Weight 457.681
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
3913
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
742
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 14.0 nM [IC50]
Inhibitor
8297
 14.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
656
Unknown

Approved Use

Unknown
Primary
Phase III
656
Unknown

Approved Use

Unknown
Primary
Phase III
656
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
781

inhibitor
1587

substrate
1737
inhibitor
1767

substrate
1037
inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
BCRP
699

CYP1A2
1524

CYP2A6
707

CYP2B6
810

CYP2C19
1478

CYP2C8
911

CYP2E1
882

P-gp
1461

UGT1A1
204

UGT2B7
146

OATP1B1
788

OATP1B3
706

OCT1
512

OCT2
647

MATE1
306

MATE2
263
BCRP
561

CYP1A2
1054

CYP2C19
991

CYP2E1
667

P-gp
1537

UGT1A1
418

UGT1A3
422
CYP1A2
701

CYP2B6
547

MATE1
6

MATE2
5

OAT1
26

OATP1B1
26

OATP1B3
6

OCT2
6
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2A6
739
 no
CYP2E1
970
 no
MATE1
308
 no
MATE2
263
 no
OCT1
543
 no
OCT2
648
 no
CYP2D6
1891
 weak [IC50 45.3 uM]
CYP2C8
965
 weak [IC50 52.1 uM]
UGT1A1
254
 weak [IC50 >100 uM]
UGT2B7
157
 weak [IC50 >100 uM]
CYP1A2
1692
 weak [IC50 >70 uM]
CYP2B6
1001
 weak [IC50 >70 uM]
CYP2C19
1553
 weak [IC50 >70 uM]
CYP2C9
1819
 weak [IC50 >70 uM]
CYP3A4
1925
 weak [IC50 >70 uM]
BCRP
773
 weak
CYP1A2
1692
 weak
CYP2B6
1001
 weak
CYP3A4
1925
 weak
MATE1
308
 weak
MATE2
263
 weak
OAT1
603
 weak
OATP1B1
803
 weak
OATP1B3
715
 weak
OCT2
648
 weak
P-gp
1650
 weak
OATP1B3
715
 yes [IC50 19 uM]
OATP1B1
803
 yes [IC50 8.76 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
BCRP
561
 weak
CYP1A2
1054
 weak
CYP2C9
1037
 weak
CYP2E1
667
 weak
P-gp
1537
 weak
UGT1A1
418
 yes
UGT1A3
422
 yes
CYP2C19
991
 yes
yes (co-administration study)
Comment: fluconazole increased selumetinib AUC by 53%
Page: 101, 107
CYP3A4
1737
 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
1647
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
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
Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification.
2012 Jul
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
6

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)
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:23:36 UTC 2023
Edited
by admin
on Fri Dec 15 16:23:36 UTC 2023
Record UNII
6UH91I579U
Record Status Validated (UNII)
Record Version
  • Download
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
SELUMETINIB [MI]
Common Name English
ARRY-886
Code English
AZD6244
Code English
Selumetinib [WHO-DD]
Common Name 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 [USAN]
Common Name English
Classification Tree Code System Code
EU-Orphan Drug EU/3/18/2050
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
NCI_THESAURUS C69145
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
NCI_THESAURUS C129825
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
FDA ORPHAN DRUG 475815
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
FDA ORPHAN DRUG 624017
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
FDA ORPHAN DRUG 471015
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
Code System Code Type Description
RXCUI
2289380
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
INN
9078
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
EPA CompTox
DTXSID3048944
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
SMS_ID
100000124313
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
CAS
606143-52-6
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
DRUG CENTRAL
5388
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
NCI_THESAURUS
C66939
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
DAILYMED
6UH91I579U
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
USAN
XX-36
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
MERCK INDEX
m12218
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
WIKIPEDIA
SELUMETINIB
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
CHEBI
90227
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
FDA UNII
6UH91I579U
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
PUBCHEM
10127622
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
DRUG BANK
DB11689
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
ChEMBL
CHEMBL1614701
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
EVMPD
SUB32237
Created by admin on Fri Dec 15 16:23:36 UTC 2023 , Edited by admin on Fri Dec 15 16:23:36 UTC 2023
PRIMARY
Related Record Type Details
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
MAJOR
CYTOCHROME P450 3A5
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 2C19
METABOLIC ENZYME -> SUBSTRATE
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
IN VITRO
BINDING
Structure of SELUMETINIB
EXCRETED UNCHANGED
After a single oral dose of radiolabeled selumetinib 75 mg (1.5 times the recommended dose) to healthy adults
AMOUNT EXCRETED
FECAL
CYTOCHROME P450 2E1
METABOLIC ENZYME -> SUBSTRATE
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A3
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 2C9
METABOLIC ENZYME -> SUBSTRATE
Structure of SELUMETINIB
EXCRETED UNCHANGED
After a single oral dose of radiolabeled selumetinib 75 mg (1.5 times the recommended dose) to healthy adults
AMOUNT EXCRETED
URINE
CYTOCHROME P450 1A2
METABOLIC ENZYME -> SUBSTRATE
DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1
TARGET -> INHIBITOR
Incorporation of [J33P]phosphate from [J33P]ATP into ERK2
UNCOMPETITIVE
IC50
DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 2
TARGET -> INHIBITOR
UNCOMPETITIVE
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> SUBSTRATE
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A1
METABOLIC ENZYME -> SUBSTRATE
Structure of SELUMETINIB SULFATE
SALT/SOLVATE -> PARENT
Related Record Type Details
Structure of 2-((6-(4-BROMO-2-CHLORO-ANILINO)-7-FLUORO-3H-BENZIMIDAZOLE-5-CARBONYL)AMINO)OXYACETIC ACID
METABOLITE -> PARENT
URINE
Structure of AZ-12791138
METABOLITE -> PARENT
FECAL; URINE
Structure of 6-(4-BROMO-2-CHLORO-ANILINO)-7-FLUORO-3H-BENZIMIDAZOLE-5-CARBOXAMIDE
METABOLITE -> PARENT
FECAL
Structure of N-DESMETHYL SELUMETINIB
METABOLITE ACTIVE -> PARENT
FECAL
Structure of AZ-133266637
METABOLITE -> PARENT
FECAL; URINE
Structure of 2-((6-(4-BROMO-2-CHLORO-ANILINO)-7-FLUORO-3H-BENZIMIDAZOLE-5-CARBONYL)AMINO)OXYACETIC ACID
METABOLITE -> PARENT
PLASMA
Structure of AZ-12791138
METABOLITE -> PARENT
PLASMA
Structure of 6-(4-BROMO-2-CHLORO-ANILINO)-7-FLUORO-3H-BENZIMIDAZOLE-5-CARBOXAMIDE
METABOLITE -> PARENT
PLASMA
Structure of AZ-133266637
METABOLITE -> PARENT
PLASMA
Structure of N-DESMETHYL SELUMETINIB
METABOLITE ACTIVE -> PARENT
N-desmethyl selumetinib represents less than 10% of selumetinib levels in human plasma, but is approximately 3 to 5 times more potent than the parent compound, contributing to about 21% to 35% of the overall pharmacologic activity.
PLASMA
Structure of N-DESMETHYL SELUMETINIB
METABOLITE ACTIVE -> PARENT
URINE
Related Record Type Details
Structure of SELUMETINIB
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC AT STEADY-STATE

IN PEDIATRIC PATIENTS

Tmax PHARMACOKINETIC IN HEALTHY ADULTS

HIGH-FAT MEAL

SINGLE DOSE ADMINISTRATION

Volume of Distribution PHARMACOKINETIC IN PEDIATRIC PATIENTS

Tmax PHARMACOKINETIC IN HEALTHY ADULTS

SINGLE DOSE ADMINISTRATION

LOW-FAT MEAL

ORAL BIOAVAILABILITY PHARMACOKINETIC IN HEALTHY ADULTS

Biological Half-life PHARMACOKINETIC
NIH
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