Details of the Drug

General Information of Drug (ID: DMC7W6R)

Drug Name
Selumetinib
Synonyms
Selumetinib; AZD-6244; ARRY142886; AZD6244; ARRY142886; AZD 6244; AZD-6244; 6UH91I579U; ARRY 142886; ARRY-142886; AZD6244 (Selumetinib); AZD6244(Selumetinib); CHEBI:90227; CHEMBL1614701; MEK inhibitors; Selumetinib (AZD6244); UNII-6UH91I579U
Indication
Disease Entry ICD 11 Status REF
Neurofibromatosis type 1 LD2D.10 Approved [1]
Melanoma 2C30 Phase 3 [2]
Thyroid cancer 2D10 Phase 3 [3]
Non-small-cell lung cancer 2C25.Y Phase 2 [4]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [5]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [5]
Solid tumour/cancer 2A00-2F9Z Investigative [6]
⏷ Show the Full List of Indication(s)
ATC Code
L01EE04: Selumetinib
L01EE: Mitogen-activated protein kinase (MEK) inhibitors
L01E: PROTEIN KINASE INHIBITORS
L01: ANTINEOPLASTIC AGENTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 457.7
Logarithm of the Partition Coefficient (xlogp) 3.6
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C17H15BrClFN4O3
IUPAC Name
6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide
Canonical SMILES
CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO
InChI
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
Cross-matching ID
PubChem CID
10127622
ChEBI ID
CHEMBL90227
CAS Number
606143-52-6
UNII
6UH91I579U
DrugBank ID
DB11689
TTD ID
D0T5DP
ACDINA ID
D01422
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
ERK activator kinase 1 (MEK1) TTIDAPM MP2K1_HUMAN Inhibitor [3]
ERK activator kinase 2 (MEK2) TTTW2NY MP2K2_HUMAN Inhibitor [3]
MAPK/ERK kinase kinase (MAP3K) TTROQ37 NOUNIPROTAC Modulator [7]
HUMAN ERK activator kinase 1 (MEK1) TTAW3TO MP2K1_HUMAN Inhibitor [5]
HUMAN ERK activator kinase 2 (MEK2) TTWX403 MP2K2_HUMAN Inhibitor [5]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Gene/Protein Processing [8]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Gene/Protein Processing [9]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Post-Translational Modifications [10]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Post-Translational Modifications [10]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Post-Translational Modifications [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

ICD Disease Classification 02 Neoplasm
Disease Class ICD-11: 2C82 Prostate cancer
The Studied Tissue Skin
The Studied Disease Melanoma [ICD-11:2C82]
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
ERK activator kinase 2 (MEK2) DTT MAP2K2 2.87E-01 0.91 0.61
ERK activator kinase 1 (MEK1) DTT MAP2K1 8.00E-01 -0.07 -0.15
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Selumetinib (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Ivosidenib DM8S6T7 Moderate Increased metabolism of Selumetinib caused by Ivosidenib mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [11]
Arn-509 DMT81LZ Major Increased metabolism of Selumetinib caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [11]
Troleandomycin DMUZNIG Major Decreased metabolism of Selumetinib caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [11]
Pexidartinib DMS2J0Z Major Increased metabolism of Selumetinib caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [11]
Osilodrostat DMIJC9X Moderate Decreased metabolism of Selumetinib caused by Osilodrostat mediated inhibition of CYP450 enzyme. Cushing syndrome [5A70] [12]
MK-8228 DMOB58Q Major Decreased metabolism of Selumetinib caused by MK-8228 mediated inhibition of CYP450 enzyme. Cytomegaloviral disease [1D82] [11]
Eslicarbazepine DMZREFQ Moderate Increased metabolism of Selumetinib caused by Eslicarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [11]
Tazemetostat DMWP1BH Moderate Increased metabolism of Selumetinib caused by Tazemetostat mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [11]
MK-1439 DM215WE Moderate Increased metabolism of Selumetinib caused by MK-1439 mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [11]
Brigatinib DM7W94S Moderate Increased metabolism of Selumetinib caused by Brigatinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [11]
PF-06463922 DMKM7EW Major Increased metabolism of Selumetinib caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [11]
Fedratinib DM4ZBK6 Major Decreased metabolism of Selumetinib caused by Fedratinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [11]
Rucaparib DM9PVX8 Moderate Decreased metabolism of Selumetinib caused by Rucaparib mediated inhibition of CYP450 enzyme. Ovarian cancer [2C73] [11]
Voxelotor DMCS6M5 Moderate Decreased metabolism of Selumetinib caused by Voxelotor mediated inhibition of CYP450 enzyme. Sickle-cell disorder [3A51] [11]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Selumetinib caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [13]
Larotrectinib DM26CQR Moderate Decreased metabolism of Selumetinib caused by Larotrectinib mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [11]
Elagolix DMB2C0E Moderate Increased metabolism of Selumetinib caused by Elagolix mediated induction of CYP450 enzyme. Uterine fibroid [2E86] [11]
⏷ Show the Full List of 17 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
FD&C blue no. 2 E00446 2723854 Colorant
Glyceryl monooleate E00473 5283468 Bioadhesive material; Emollient; Emulsifying agent; Emulsion stabilizing agent; Gelling agent; Modified-release agent; Surfactant
Potassium chloride E00074 4873 Tonicity agent
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Ferric oxide black E00522 16211978 Colorant
Hypromellose E00634 Not Available Coating agent
Propylene glycol E00040 1030 Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Tocophersolan E00679 Not Available Antioxidant; Binding agent; Emulsifying agent; Ointment base; Solubilizing agent; Surfactant; Suspending agent
Water E00035 962 Solvent
Haematite red E00236 14833 Colorant
Ammonium hydroxide E00687 Not Available Alkalizing agent
Carrageenan E00714 Not Available Emulsion stabilizing agent; Gelling agent; Microencapsulating agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Pregelatinized starch E00674 Not Available Binding agent; Diluent; Disintegrant
Shellac E00695 Not Available Coating agent; Film/membrane-forming agent; Microencapsulating agent; Modified-release agent
⏷ Show the Full List of 15 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Selumetinib 25 mg capsule 25 mg Capsule Oral
Selumetinib 10 mg capsule 10 mg Capsule Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2 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)
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5665).
5 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
6 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1479).
7 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.
8 Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification. Mol Cancer Ther. 2012 Jul;11(7):1557-64. doi: 10.1158/1535-7163.MCT-11-0934. Epub 2012 Jun 22.
9 Ursonic acid exerts inhibitory effects on matrix metalloproteinases via ERK signaling pathway. Chem Biol Interact. 2020 Jan 5;315:108910. doi: 10.1016/j.cbi.2019.108910. Epub 2019 Nov 29.
10 The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition. Br J Cancer. 2012 Apr 10;106(8):1386-94. doi: 10.1038/bjc.2012.70. Epub 2012 Mar 13.
11 Product Information. Koselugo (selumetinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
12 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
13 Multum Information Services, Inc. Expert Review Panel.