Drug Details

General Information of the Drug (ID: DR6609)
Name
Selumetinib
Synonyms
Selumetinib; 606143-52-6; AZD6244; AZD 6244; ARRY-142886; 5-[(4-BROMO-2-CHLOROPHENYL)AMINO]-4-FLUORO-N-(2-HYDROXYETHOXY)-1-METHYL-1H-BENZIMIDAZOLE-6-CARBOXAMIDE; AZD-6244; Selumetinib (AZD6244); ARRY 142886; AZD6244 (Selumetinib); ARRY-886; UNII-6UH91I579U; 5-((4-bromo-2-chlorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzo[d]imidazole-6-carboxamide; 5-(4-broMo-2-chlorophenylaMino)-4-fluoro-N-(2-hydroxyethoxy)-1-Methyl-1H-benzo[d]iMidazole-6-carboxaMide; CHEMBL1614701; CHEBI:90227; 6UH91I579U; NCGC00189073-01; NCGC00189073-02; C17H15BrClFN4O3; DSSTox_CID_28870; DSSTox_RID_83139; DSSTox_GSID_48944; 1H-Benzimidazole-6-carboxamide, 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-; 6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide; 6-[(4-bromo-2-chlorophenyl)amino]-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide; AZD 6244;5-((4-Bromo-2-chlorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzo[d]imidazole-6-carboxamide;6-(4-bromo-2-chlorophenylamino)-7-fluoro-N-(2-hydroxyethoxy)-3-methyl-3H-benzo[d]imidazole-5-carboxamide; CAS-606143-52-6; ARRY142886; AZD6244(Selumetinib); Selumetinib [USAN:INN]; selumetinibum; Koselugo; 1H-Benzimidazole-6-carboxamide, 5-((4-bromo-2-chlorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-; 3EW; PubChem21092; AZD 6244 Selumetinib; Selumetinib (USAN/INN); AZD-6244(Selumetinib); AZD6244 - Selumetinib; AZD 6244 (Selumetinib); SCHEMBL155456; GTPL5665; QCR-91; Selumetinib, ARRY-142886; DTXSID3048944; EX-A020; SYN1016; BCPP000367; CC-49; HMS3244G03; HMS3244G04; HMS3244H03; HMS3265K01; HMS3265K02; HMS3265L01; HMS3265L02; HMS3654O03; NSC 741O78; AOB87732; BCP01739; Tox21_113362; ABP000918; ANW-45526; BDBM50355497; MFCD11977472; NSC741078; NSC800882; s1008; ZINC31773258; ARRY142886/AZD6244; AKOS015904255; Tox21_113362_1; ACN-031539; BCP9000354; CCG-264774; CS-0059; DB11689; EX-8621; NSC-741078; NSC-800882; SB14707; NCGC00189073-07; AC-25059; AK-40782; AM808016; AZD6244,Selumetinib, ARRY-142886; BC004624; HY-50706; AZD6244 (Selumetinib,ARRY-142886); AB0007973; FT-0674552; SW202561-3; X2640; D09666; S-7764; 143A526; Q-101405; Q7448840; BRD-K57080016-001-01-9; 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-1,3-benzodiazole-6-carboxamide; 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy -ethoxy)-amide; 6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide; 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid(2-hydroxy-ethoxy)-amide; 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethoxy)-amide; 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid(2-hydroxyethoxy)-amide; 6-(4-bromo-2-chlorophenylamino)-N-(2-hydroxyethoxy)-3,7-dimethyl-3H-benzo[d]imidazole-5-carboxamide; 6-(4-bromo-2chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide
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Molecular Type
Small molecule
Disease Melanoma [ICD-11: 2C30] Phase 3 [1]
Structure
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2D MOL

3D MOL

ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 145-228 mgh/L
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 26.1 mg/L
Bioavailability
The bioavailability of drug is 34-58%
Clearance
The clearance of drug is 8.8 L/h
Elimination
Approximately 59% of selumetinib is eliminated in the feces, while 33% is eliminated in the urine
Half-life
The concentration or amount of drug in body reduced by one-half in 6.2 hours (in pediatric patients)
Metabolism
The drug is metabolized via the liver
Vd
The volume of distribution (Vd) of drug is 78-171 L
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C17H15BrClFN4O3
PubChem CID
10127622
Canonical SMILES
CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO
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)
InChIKey
CYOHGALHFOKKQC-UHFFFAOYSA-N
CAS Number
CAS 606143-52-6
ChEBI ID
CHEBI:90227
TTD Drug ID
D0T5DP
DrugBank ID
DB11689
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Glucocorticoids      Homo sapiens     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BCL2L11  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
                    In-vitro Model Cells derived from acute lymphoblastic leukemia patients Acute lymphoblastic leukemia Homo sapiens
                    In-vivo Model For a xenograft model, primagraft cells were injected intrafemorally into NOD SCID Gamma null (NSG) mice.
                    Experimental
                    Result(s)		 A selumetinib-dexamethasone combination may be highly effective in RAS pathway-mutated acute lymphoblastic leukemia.
Target and Pathway
Target(s) ERK activator kinase 1 (MEK1)  Molecule Info  [3]
ERK activator kinase 2 (MEK2)  Molecule Info  [3]
MAPK/ERK kinase kinase (MAP3K)  Molecule Info  [4]
KEGG Pathway MAPK signaling pathway Click to Show/Hide
2 ErbB signaling pathway
3 Ras signaling pathway
4 Rap1 signaling pathway
5 cGMP-PKG signaling pathway
6 cAMP signaling pathway
7 Chemokine signaling pathway
8 HIF-1 signaling pathway
9 FoxO signaling pathway
10 Sphingolipid signaling pathway
11 Oocyte meiosis
12 PI3K-Akt signaling pathway
13 Vascular smooth muscle contraction
14 Dorso-ventral axis formation
15 VEGF signaling pathway
16 Osteoclast differentiation
17 Focal adhesion
18 Gap junction
19 Signaling pathways regulating pluripotency of stem cells
20 Toll-like receptor signaling pathway
21 Natural killer cell mediated cytotoxicity
22 T cell receptor signaling pathway
23 B cell receptor signaling pathway
24 Fc epsilon RI signaling pathway
25 Fc gamma R-mediated phagocytosis
26 TNF signaling pathway
27 Long-term potentiation
28 Neurotrophin signaling pathway
29 Cholinergic synapse
30 Serotonergic synapse
31 Long-term depression
32 Regulation of actin cytoskeleton
33 Insulin signaling pathway
34 GnRH signaling pathway
35 Progesterone-mediated oocyte maturation
36 Estrogen signaling pathway
37 Melanogenesis
38 Prolactin signaling pathway
39 Thyroid hormone signaling pathway
40 Oxytocin signaling pathway
41 Prion diseases
42 Alcoholism
43 Hepatitis B
44 Influenza A
45 Pathways in cancer
46 Proteoglycans in cancer
47 MicroRNAs in cancer
48 Colorectal cancer
49 Renal cell carcinoma
50 Pancreatic cancer
51 Endometrial cancer
52 Glioma
53 Prostate cancer
54 Thyroid cancer
55 Melanoma
56 Bladder cancer
57 Chronic myeloid leukemia
58 Acute myeloid leukemia
59 Non-small cell lung cancer
60 Central carbon metabolism in cancer
61 Choline metabolism in cancer
NetPath Pathway FSH Signaling Pathway Click to Show/Hide
2 TGF_beta_Receptor Signaling Pathway
Panther Pathway Angiogenesis Click to Show/Hide
2 B cell activation
3 EGF receptor signaling pathway
4 Endothelin signaling pathway
5 FGF signaling pathway
6 Insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade
7 Integrin signalling pathway
8 PDGF signaling pathway
9 T cell activation
10 Toll receptor signaling pathway
11 VEGF signaling pathway
12 Ras Pathway
13 Angiotensin II-stimulated signaling through G proteins and beta-arrestin
14 CCKR signaling map ST
Pathwhiz Pathway Fc Epsilon Receptor I Signaling in Mast Cells Click to Show/Hide
2 Insulin Signalling
3 Intracellular Signalling Through Adenosine Receptor A2a and Adenosine
4 Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
Pathway Interaction Database Fc-epsilon receptor I signaling in mast cells Click to Show/Hide
2 Endothelins
3 BCR signaling pathway
4 GMCSF-mediated signaling events
5 Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
6 EPHB forward signaling
7 SHP2 signaling
8 Netrin-mediated signaling events
9 mTOR signaling pathway
10 Class IB PI3K non-lipid kinase events
11 IL2-mediated signaling events
12 Ras signaling in the CD4+ TCR pathway
13 Ceramide signaling pathway
14 IFN-gamma pathway
15 ErbB1 downstream signaling
16 ErbB2/ErbB3 signaling events
17 FOXM1 transcription factor network
18 PDGFR-beta signaling pathway
19 Neurotrophic factor-mediated Trk receptor signaling
20 Nongenotropic Androgen signaling
21 Hedgehog signaling events mediated by Gli proteins
22 CXCR3-mediated signaling events
23 Signaling events mediated by Stem cell factor receptor (c-Kit)
24 Signaling events mediated by VEGFR1 and VEGFR2
25 Cellular roles of Anthrax toxin
26 Trk receptor signaling mediated by the MAPK pathway
27 Downstream signaling in na&#xef
28
29 Signaling events mediated by focal adhesion kinase
Reactome MAPK3 (ERK1) activation Click to Show/Hide
2 Uptake and function of anthrax toxins
3 RAF activation
4 MAP2K and MAPK activation
5 Negative feedback regulation of MAPK pathway
6 MAP3K8 (TPL2)-dependent MAPK1/3 activation
7 MAPK1 (ERK2) activation
WikiPathways Toll-like receptor signaling pathway Click to Show/Hide
2 Serotonin Receptor 4/6/7 and NR3C Signaling
3 Serotonin Receptor 2 and ELK-SRF/GATA4 signaling
4 Serotonin HTR1 Group and FOS Pathway
5 Estrogen signaling pathway
6 TCR Signaling Pathway
7 ErbB Signaling Pathway
8 Hypothetical Network for Drug Addiction
9 Senescence and Autophagy in Cancer
10 EPO Receptor Signaling
11 Regulation of Actin Cytoskeleton
12 IL-2 Signaling Pathway
13 Insulin Signaling
14 EGF/EGFR Signaling Pathway
15 MAPK Cascade
16 MAPK Signaling Pathway
17 TGF beta Signaling Pathway
18 IL-6 signaling pathway
19 Signaling of Hepatocyte Growth Factor Receptor
20 Focal Adhesion
21 Kit receptor signaling pathway
22 IL-3 Signaling Pathway
23 Bladder Cancer
24 Cardiac Hypertrophic Response
25 MAP kinase activation in TLR cascade
26 RAF/MAP kinase cascade
27 Nanoparticle-mediated activation of receptor signaling
28 Structural Pathway of Interleukin 1 (IL-1)
29 Genes and (Common) Pathways Underlying Drug Addiction
30 Nifedipine Activity
31 Aryl Hydrocarbon Receptor
32 PDGF Pathway
33 BDNF signaling pathway
34 Integrated Pancreatic Cancer Pathway
35 Oncostatin M Signaling Pathway
36 Corticotropin-releasing hormone
37 Interleukin-11 Signaling Pathway
38 AGE/RAGE pathway
39 B Cell Receptor Signaling Pathway
40 Prostate Cancer
41 Signaling Pathways in Glioblastoma
42 TSLP Signaling Pathway
43 IL-9 Signaling Pathway
44 Endothelin Pathways
45 IL-7 Signaling Pathway
46 Leptin signaling pathway
47 TSH signaling pathway
48 RANKL/RANK Signaling Pathway
49 IL-1 signaling pathway
50 Signaling by FGFR
51 Integrin-mediated Cell Adhesion
52 L1CAM interactions
53 MicroRNAs in cardiomyocyte hypertrophy
54 Regulation of toll-like receptor signaling pathway
55 Osteopontin Signaling
56 IL-5 Signaling Pathway
57 Amyotrophic lateral sclerosis (ALS)
References
Reference 1 ClinicalTrials.gov (NCT01933932) Assess Efficacy & Safety of Selumetinib in Combination With Docetaxel in Patients Receiving 2nd Line Treatment for v-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Positive NSCLC (SELECT-1)
Reference 2 Glucocorticoids and selumetinib are highly synergistic in RAS pathway-mutated childhood acute lymphoblastic leukemia through upregulation of BIM. Haematologica. 2019 Sep;104(9):1804-1811.
Reference 3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Reference 4 Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by cAMP-dependent protein kinase A activation in human lung and colorectal cancer cells.Br J Cancer.2012 May 8;106(10):1648-59.
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