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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:: 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%)

data_source:
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
experiment_type: steady
dose_type: Recommended
co-adm with
    data_source:
    https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
    unhealthy, 10.2 years (range: 3.5 - 17.4 years)
    population: unhealthy
    age: 10.2 years (range: 3.5 - 17.4 years)
    sex: M+F
    food_status:
    n:
    data_source:
    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)

    data_source:
    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
    experiment_type: steady
    dose_type:
    co-adm with
      data_source:
      https://pubmed.ncbi.nlm.nih.gov/20179232
      unhealthy, 57.9 years (range: 30-76 years)
      population: unhealthy
      age: 57.9 years (range: 30-76 years)
      sex: M+F
      food_status:
      n:
      data_source:
      https://pubmed.ncbi.nlm.nih.gov/20179232
      DLT: Acneiform dermatitis, Pleural effusion...
      Dose limiting toxicities:
      Acneiform dermatitis (grade 3)
      Pleural effusion (grade 3)

      data_source:
      https://pubmed.ncbi.nlm.nih.gov/20179232
      75 mg 2 times / day steady, oral
      dose: 75 mg 2 times / day
      route: oral
      experiment_type: steady
      dose_type:
      co-adm with
        data_source:
        https://pubmed.ncbi.nlm.nih.gov/20179232
        unhealthy, 57.9 years (range: 30-76 years)
        population: unhealthy
        age: 57.9 years (range: 30-76 years)
        sex: M+F
        food_status:
        n:
        data_source:
        https://pubmed.ncbi.nlm.nih.gov/20179232
        DLT: Fatigue...
        Dose limiting toxicities:
        Fatigue (grade 3)

        data_source:
        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
        experiment_type: steady
        dose_type: Highest studied dose
        co-adm with
          data_source:
          https://pubmed.ncbi.nlm.nih.gov/18390968
          unhealthy, 58 years (range: 29–78 years)
          population: unhealthy
          age: 58 years (range: 29–78 years)
          sex: M+F
          food_status:
          n:
          data_source:
          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)

          data_source:
          https://pubmed.ncbi.nlm.nih.gov/18390968
          AEs

          AEs

          AESignificanceDosePopulation
          Acneiform dermatitis grade 3
          DLT
          100 mg 2 times / day steady, oral
          dose: 100 mg 2 times / day
          route: oral
          experiment_type: steady
          dose_type:
          co-adm with
            data_source:
            https://pubmed.ncbi.nlm.nih.gov/20179232
            unhealthy, 57.9 years (range: 30-76 years)
            population:
            age:
            sex:
            food_status:
            n:
            data_source:
            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
            experiment_type: steady
            dose_type:
            co-adm with
              data_source:
              https://pubmed.ncbi.nlm.nih.gov/20179232
              unhealthy, 57.9 years (range: 30-76 years)
              population:
              age:
              sex:
              food_status:
              n:
              data_source:
              https://pubmed.ncbi.nlm.nih.gov/20179232
              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
              experiment_type: steady
              dose_type: Recommended
              co-adm with
                data_source:
                https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
                unhealthy, 10.2 years (range: 3.5 - 17.4 years)
                population:
                age:
                sex:
                food_status:
                n:
                data_source:
                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
                experiment_type: steady
                dose_type: Recommended
                co-adm with
                  data_source:
                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
                  unhealthy, 10.2 years (range: 3.5 - 17.4 years)
                  population:
                  age:
                  sex:
                  food_status:
                  n:
                  data_source:
                  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
                  experiment_type: steady
                  dose_type: Recommended
                  co-adm with
                    data_source:
                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
                    unhealthy, 10.2 years (range: 3.5 - 17.4 years)
                    population:
                    age:
                    sex:
                    food_status:
                    n:
                    data_source:
                    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
                    experiment_type: steady
                    dose_type: Recommended
                    co-adm with
                      data_source:
                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
                      unhealthy, 10.2 years (range: 3.5 - 17.4 years)
                      population:
                      age:
                      sex:
                      food_status:
                      n:
                      data_source:
                      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
                      experiment_type: steady
                      dose_type: Recommended
                      co-adm with
                        data_source:
                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
                        unhealthy, 10.2 years (range: 3.5 - 17.4 years)
                        population:
                        age:
                        sex:
                        food_status:
                        n:
                        data_source:
                        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
                        experiment_type: steady
                        dose_type: Recommended
                        co-adm with
                          data_source:
                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
                          unhealthy, 10.2 years (range: 3.5 - 17.4 years)
                          population:
                          age:
                          sex:
                          food_status:
                          n:
                          data_source:
                          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
                          experiment_type: steady
                          dose_type: Recommended
                          co-adm with
                            data_source:
                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
                            unhealthy, 10.2 years (range: 3.5 - 17.4 years)
                            population:
                            age:
                            sex:
                            food_status:
                            n:
                            data_source:
                            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
                            experiment_type: steady
                            dose_type: Recommended
                            co-adm with
                              data_source:
                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
                              unhealthy, 10.2 years (range: 3.5 - 17.4 years)
                              population:
                              age:
                              sex:
                              food_status:
                              n:
                              data_source:
                              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
                              experiment_type: steady
                              dose_type: Recommended
                              co-adm with
                                data_source:
                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
                                unhealthy, 10.2 years (range: 3.5 - 17.4 years)
                                population:
                                age:
                                sex:
                                food_status:
                                n:
                                data_source:
                                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
                                experiment_type: steady
                                dose_type: Recommended
                                co-adm with
                                  data_source:
                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
                                  unhealthy, 10.2 years (range: 3.5 - 17.4 years)
                                  population:
                                  age:
                                  sex:
                                  food_status:
                                  n:
                                  data_source:
                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
                                  Fatigue grade 1-2,2 pts%
                                  300 mg 2 times / day steady, oral
                                  Highest studied dose
                                  dose: 300 mg 2 times / day
                                  route: oral
                                  experiment_type: steady
                                  dose_type: Highest studied dose
                                  co-adm with
                                    data_source:
                                    https://pubmed.ncbi.nlm.nih.gov/18390968
                                    unhealthy, 58 years (range: 29–78 years)
                                    population:
                                    age:
                                    sex:
                                    food_status:
                                    n:
                                    data_source:
                                    https://pubmed.ncbi.nlm.nih.gov/18390968
                                    Peripheral edema grade 1-2,2 pts%
                                    300 mg 2 times / day steady, oral
                                    Highest studied dose
                                    dose: 300 mg 2 times / day
                                    route: oral
                                    experiment_type: steady
                                    dose_type: Highest studied dose
                                    co-adm with
                                      data_source:
                                      https://pubmed.ncbi.nlm.nih.gov/18390968
                                      unhealthy, 58 years (range: 29–78 years)
                                      population:
                                      age:
                                      sex:
                                      food_status:
                                      n:
                                      data_source:
                                      https://pubmed.ncbi.nlm.nih.gov/18390968
                                      Vomiting grade 1-2,2 pts%
                                      300 mg 2 times / day steady, oral
                                      Highest studied dose
                                      dose: 300 mg 2 times / day
                                      route: oral
                                      experiment_type: steady
                                      dose_type: Highest studied dose
                                      co-adm with
                                        data_source:
                                        https://pubmed.ncbi.nlm.nih.gov/18390968
                                        unhealthy, 58 years (range: 29–78 years)
                                        population:
                                        age:
                                        sex:
                                        food_status:
                                        n:
                                        data_source:
                                        https://pubmed.ncbi.nlm.nih.gov/18390968
                                        Blurred vision grade 1-2,3 pts%
                                        300 mg 2 times / day steady, oral
                                        Highest studied dose
                                        dose: 300 mg 2 times / day
                                        route: oral
                                        experiment_type: steady
                                        dose_type: Highest studied dose
                                        co-adm with
                                          data_source:
                                          https://pubmed.ncbi.nlm.nih.gov/18390968
                                          unhealthy, 58 years (range: 29–78 years)
                                          population:
                                          age:
                                          sex:
                                          food_status:
                                          n:
                                          data_source:
                                          https://pubmed.ncbi.nlm.nih.gov/18390968
                                          Nausea grade 1-2,3 pts%
                                          300 mg 2 times / day steady, oral
                                          Highest studied dose
                                          dose: 300 mg 2 times / day
                                          route: oral
                                          experiment_type: steady
                                          dose_type: Highest studied dose
                                          co-adm with
                                            data_source:
                                            https://pubmed.ncbi.nlm.nih.gov/18390968
                                            unhealthy, 58 years (range: 29–78 years)
                                            population:
                                            age:
                                            sex:
                                            food_status:
                                            n:
                                            data_source:
                                            https://pubmed.ncbi.nlm.nih.gov/18390968
                                            Diarrhea grade 3-4,1 pts%
                                            300 mg 2 times / day steady, oral
                                            Highest studied dose
                                            dose: 300 mg 2 times / day
                                            route: oral
                                            experiment_type: steady
                                            dose_type: Highest studied dose
                                            co-adm with
                                              data_source:
                                              https://pubmed.ncbi.nlm.nih.gov/18390968
                                              unhealthy, 58 years (range: 29–78 years)
                                              population:
                                              age:
                                              sex:
                                              food_status:
                                              n:
                                              data_source:
                                              https://pubmed.ncbi.nlm.nih.gov/18390968
                                              Dermatitis acneiform grade 3-4,2 pts%
                                              300 mg 2 times / day steady, oral
                                              Highest studied dose
                                              dose: 300 mg 2 times / day
                                              route: oral
                                              experiment_type: steady
                                              dose_type: Highest studied dose
                                              co-adm with
                                                data_source:
                                                https://pubmed.ncbi.nlm.nih.gov/18390968
                                                unhealthy, 58 years (range: 29–78 years)
                                                population:
                                                age:
                                                sex:
                                                food_status:
                                                n:
                                                data_source:
                                                https://pubmed.ncbi.nlm.nih.gov/18390968
                                                Rash erythematous grade 3-4,2 pts%
                                                300 mg 2 times / day steady, oral
                                                Highest studied dose
                                                dose: 300 mg 2 times / day
                                                route: oral
                                                experiment_type: steady
                                                dose_type: Highest studied dose
                                                co-adm with
                                                  data_source:
                                                  https://pubmed.ncbi.nlm.nih.gov/18390968
                                                  unhealthy, 58 years (range: 29–78 years)
                                                  population:
                                                  age:
                                                  sex:
                                                  food_status:
                                                  n:
                                                  data_source:
                                                  https://pubmed.ncbi.nlm.nih.gov/18390968
                                                  Rash maculo-papular grade 3-4,2 pts%
                                                  300 mg 2 times / day steady, oral
                                                  Highest studied dose
                                                  dose: 300 mg 2 times / day
                                                  route: oral
                                                  experiment_type: steady
                                                  dose_type: Highest studied dose
                                                  co-adm with
                                                    data_source:
                                                    https://pubmed.ncbi.nlm.nih.gov/18390968
                                                    unhealthy, 58 years (range: 29–78 years)
                                                    population:
                                                    age:
                                                    sex:
                                                    food_status:
                                                    n:
                                                    data_source:
                                                    https://pubmed.ncbi.nlm.nih.gov/18390968
                                                    Rash pruritic grade 3-4,2 pts%
                                                    300 mg 2 times / day steady, oral
                                                    Highest studied dose
                                                    dose: 300 mg 2 times / day
                                                    route: oral
                                                    experiment_type: steady
                                                    dose_type: Highest studied dose
                                                    co-adm with
                                                      data_source:
                                                      https://pubmed.ncbi.nlm.nih.gov/18390968
                                                      unhealthy, 58 years (range: 29–78 years)
                                                      population:
                                                      age:
                                                      sex:
                                                      food_status:
                                                      n:
                                                      data_source:
                                                      https://pubmed.ncbi.nlm.nih.gov/18390968
                                                      Rash grade 3-4,2 pts%
                                                      300 mg 2 times / day steady, oral
                                                      Highest studied dose
                                                      dose: 300 mg 2 times / day
                                                      route: oral
                                                      experiment_type: steady
                                                      dose_type: Highest studied dose
                                                      co-adm with
                                                        data_source:
                                                        https://pubmed.ncbi.nlm.nih.gov/18390968
                                                        unhealthy, 58 years (range: 29–78 years)
                                                        population:
                                                        age:
                                                        sex:
                                                        food_status:
                                                        n:
                                                        data_source:
                                                        https://pubmed.ncbi.nlm.nih.gov/18390968
                                                        Fatigue grade 3
                                                        DLT
                                                        75 mg 2 times / day steady, oral
                                                        dose: 75 mg 2 times / day
                                                        route: oral
                                                        experiment_type: steady
                                                        dose_type:
                                                        co-adm with
                                                          data_source:
                                                          https://pubmed.ncbi.nlm.nih.gov/20179232
                                                          unhealthy, 57.9 years (range: 30-76 years)
                                                          population:
                                                          age:
                                                          sex:
                                                          food_status:
                                                          n:
                                                          data_source:
                                                          https://pubmed.ncbi.nlm.nih.gov/20179232
                                                          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
                                                          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

                                                          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)
                                                          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