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Details

Stereochemistry ACHIRAL
Molecular Formula C17H15BrClFN4O3.H2O4S
Molecular Weight 555.7611
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SELUMETINIB SULFATE

SMILES

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

InChI

InChIKey=GRKFGZYYYYISDX-UHFFFAOYSA-N
InChI=1S/C17H15BrClFN4O3.H2O4S/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;1-5(2,3)4/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26);(H2,1,2,3,4)

HIDE SMILES / InChI

Molecular Formula C17H15BrClFN4O3
Molecular Weight 457.6815
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula H2O4S
Molecular Weight 98.0796
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: 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

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.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
647 ng/mL
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
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
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%
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
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
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:
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:
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Sources:
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:
100 mg 2 times / day steady, oral
Dose: 100 mg, 2 times / day
Route: oral
Route: steady
Dose: 100 mg, 2 times / day
Sources:
unhealthy, 57.9 years (range: 30-76 years)
Health Status: unhealthy
Age Group: 57.9 years (range: 30-76 years)
Sex: M+F
Sources:
DLT: Acneiform dermatitis, Pleural effusion...
Dose limiting toxicities:
Acneiform dermatitis (grade 3)
Pleural effusion (grade 3)
Sources:
75 mg 2 times / day steady, oral
Dose: 75 mg, 2 times / day
Route: oral
Route: steady
Dose: 75 mg, 2 times / day
Sources:
unhealthy, 57.9 years (range: 30-76 years)
Health Status: unhealthy
Age Group: 57.9 years (range: 30-76 years)
Sex: M+F
Sources:
DLT: Fatigue...
Dose limiting toxicities:
Fatigue (grade 3)
Sources:
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:
unhealthy, 58 years (range: 29–78 years)
Health Status: unhealthy
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Sources:
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:
AEs

AEs

AESignificanceDosePopulation
Acute kidney injury 2%
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Creatinine increased 2%
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Diarrhea 2%
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Malignant peripheral nerve sheath tumor 2%
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Paronychia 2%
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Skin ulcer 2%
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Weight increased 2%
Disc. AE
25 mg/m2 2 times / day steady, oral
Recommended
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
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:
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Sources:
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:
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Sources:
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:
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Sources:
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:
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Sources:
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:
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Sources:
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:
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Sources:
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:
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Sources:
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:
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Sources:
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:
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Sources:
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:
unhealthy, 10.2 years (range: 3.5 - 17.4 years)
Health Status: unhealthy
Age Group: 10.2 years (range: 3.5 - 17.4 years)
Sex: M+F
Sources:
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:
unhealthy, 57.9 years (range: 30-76 years)
Health Status: unhealthy
Age Group: 57.9 years (range: 30-76 years)
Sex: M+F
Sources:
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:
unhealthy, 57.9 years (range: 30-76 years)
Health Status: unhealthy
Age Group: 57.9 years (range: 30-76 years)
Sex: M+F
Sources:
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:
unhealthy, 57.9 years (range: 30-76 years)
Health Status: unhealthy
Age Group: 57.9 years (range: 30-76 years)
Sex: M+F
Sources:
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:
unhealthy, 58 years (range: 29–78 years)
Health Status: unhealthy
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Sources:
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:
unhealthy, 58 years (range: 29–78 years)
Health Status: unhealthy
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Sources:
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:
unhealthy, 58 years (range: 29–78 years)
Health Status: unhealthy
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Sources:
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:
unhealthy, 58 years (range: 29–78 years)
Health Status: unhealthy
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Sources:
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:
unhealthy, 58 years (range: 29–78 years)
Health Status: unhealthy
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Sources:
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:
unhealthy, 58 years (range: 29–78 years)
Health Status: unhealthy
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Sources:
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:
unhealthy, 58 years (range: 29–78 years)
Health Status: unhealthy
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Sources:
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:
unhealthy, 58 years (range: 29–78 years)
Health Status: unhealthy
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Sources:
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:
unhealthy, 58 years (range: 29–78 years)
Health Status: unhealthy
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Sources:
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:
unhealthy, 58 years (range: 29–78 years)
Health Status: unhealthy
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Sources:
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:
unhealthy, 58 years (range: 29–78 years)
Health Status: unhealthy
Age Group: 58 years (range: 29–78 years)
Sex: M+F
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
weak [IC50 45.3 uM]
weak [IC50 52.1 uM]
weak [IC50 >100 uM]
weak [IC50 >100 uM]
weak [IC50 >70 uM]
weak [IC50 >70 uM]
weak [IC50 >70 uM]
weak [IC50 >70 uM]
weak [IC50 >70 uM]
weak
weak
weak
weak
weak
weak
weak
weak
weak
weak
weak
yes [IC50 19 uM]
yes [IC50 8.76 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
weak
weak
weak
weak
weak
yes
yes
yes
yes (co-administration study)
Comment: fluconazole increased selumetinib AUC by 53%
Page: 101, 107
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

PubMed

PubMed

TitleDatePubMed
Targeted inhibition of the extracellular signal-regulated kinase kinase pathway with AZD6244 (ARRY-142886) in the treatment of hepatocellular carcinoma.
2007 Jan
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
The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition.
2012 Apr 10
Synergistic induction of human cathelicidin antimicrobial peptide gene expression by vitamin D and stilbenoids.
2014 Mar
Patents

Sample Use Guides

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
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 Sat Jun 26 12:30:44 UTC 2021
Edited
by admin
on Sat Jun 26 12:30:44 UTC 2021
Record UNII
807ME4B7IJ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SELUMETINIB SULFATE
USAN   WHO-DD  
USAN  
Official Name English
1H-BENZIMIDAZOLE-6-CARBOXAMIDE, 5-((4-BROMO-2-CHLOROPHENYL)AMINO)-4-FLUORO-N-(2- HYDROXYETHOXY)-1-METHYL-, SULFATE (1:1)
Systematic Name English
KOSELUGO
Brand Name English
AZD6244 HYDROGEN SULPHATE
Common Name English
5-((4-BROMO-2-CHLOROPHENYL)AMINO)-4-FLUORO-N-(2-HYDROXYETHOXY)-1-METHYL-1H- BENZIMIDAZOLE-6-CARBOXAMIDE SULFATE
Systematic Name English
SELUMETINIB SULFATE [WHO-DD]
Common Name English
SELUMETINIB SULFATE [JAN]
Common Name English
1H-BENZIMIDAZOLE-6-CARBOXAMIDE, 5-((4-BROMO-2-CHLOROPHENYL)AMINO)-4-FLUORO-N-(2- HYDROXYETHOXY)-1-METHYL-, SULPHATE (1:1)
Systematic Name English
SELUMETINIB SULPHATE
Common Name English
AZD6244 HYDROGEN SULFATE
Code English
AZD-6244 HYDROGEN SULPHATE
Common Name English
AZD-6244 HYDROGEN SULFATE
Code English
SELUMETINIB SULFATE [USAN]
Common Name English
AZD-6244 HYD-SULFATE
Code English
5-((4-BROMO-2-CHLOROPHENYL)AMINO)-4-FLUORO-N-(2-HYDROXYETHOXY)-1-METHYL-1H- BENZIMIDAZOLE-6-CARBOXAMIDE SULPHATE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C69145
Created by admin on Sat Jun 26 12:30:45 UTC 2021 , Edited by admin on Sat Jun 26 12:30:45 UTC 2021
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 12:30:45 UTC 2021 , Edited by admin on Sat Jun 26 12:30:45 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL1614701
Created by admin on Sat Jun 26 12:30:44 UTC 2021 , Edited by admin on Sat Jun 26 12:30:44 UTC 2021
PRIMARY
EVMPD
SUB36237
Created by admin on Sat Jun 26 12:30:44 UTC 2021 , Edited by admin on Sat Jun 26 12:30:44 UTC 2021
PRIMARY
EPA CompTox
943332-08-9
Created by admin on Sat Jun 26 12:30:45 UTC 2021 , Edited by admin on Sat Jun 26 12:30:45 UTC 2021
PRIMARY
CAS
943332-08-9
Created by admin on Sat Jun 26 12:30:44 UTC 2021 , Edited by admin on Sat Jun 26 12:30:44 UTC 2021
PRIMARY
RXCUI
2361596
Created by admin on Sat Jun 26 12:30:45 UTC 2021 , Edited by admin on Sat Jun 26 12:30:45 UTC 2021
PRIMARY
FDA UNII
807ME4B7IJ
Created by admin on Sat Jun 26 12:30:45 UTC 2021 , Edited by admin on Sat Jun 26 12:30:45 UTC 2021
PRIMARY
NCI_THESAURUS
C95225
Created by admin on Sat Jun 26 12:30:45 UTC 2021 , Edited by admin on Sat Jun 26 12:30:45 UTC 2021
PRIMARY
PUBCHEM
16214875
Created by admin on Sat Jun 26 12:30:45 UTC 2021 , Edited by admin on Sat Jun 26 12:30:45 UTC 2021
PRIMARY
DRUG BANK
DBSALT002048
Created by admin on Sat Jun 26 12:30:45 UTC 2021 , Edited by admin on Sat Jun 26 12:30:45 UTC 2021
PRIMARY
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