3EW

5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide



Chemical Component Summary

Name5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide
SynonymsSelumetinib
Identifiers6-[(4-bromanyl-2-chloranyl-phenyl)amino]-7-fluoranyl-N-(2-hydroxyethyloxy)-3-methyl-benzimidazole-5-carboxamide
FormulaC17 H15 Br Cl F N4 O3
Molecular Weight457.681
TypeNON-POLYMER
Isomeric SMILESCn1cnc2c1cc(c(c2F)Nc3ccc(cc3Cl)Br)C(=O)NOCCO
InChIInChI=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)
InChIKeyCYOHGALHFOKKQC-UHFFFAOYSA-N

Chemical Details

Formal Charge0
Atom Count42
Chiral Atom Count0
Bond Count44
Aromatic Bond Count16

Drug Info: DrugBank

DrugBank IDDB11689 
NameSelumetinib
Groups
  • approved
  • investigational
DescriptionActivation of the Raf-MEK-ERK signalling pathway is known to be implemented in several types of malignancies; thus, mitogen-activated protein kinase kinase (MEK) inhibitors such as selumetinib are important tools that can target the problematic overactivity of this pathway.[A193611] Results from clinical trials investigating earlier developed MEK inhibitors were underwhelming.[A193611] However, selumetinib demonstrated impressive efficacy and tolerability in Phase I trials, leading to its continued investigation for the treatment of various types of tumours in Phase II trials.[A193611] Currently, the novel MEK 1 / 2 inhibitor, selumetinib, is approved solely for the treatment of Neurofibromatosis type 1 (NF-1) in a limited age group. NF-1 is considered rare, with an estimated incidence of 1/3000 individuals.[A193608] It is a genetic, autosomal dominant condition resulting from mutations of the NF1 gene, which can lead to various complications, including the development of multiple tumours in the nervous system.[A193533,A193608] Some patients with this disorder develop plexiform neurofibromas (PN); however, this is considered relatively uncommon compared to other variants of NF-1.[A193608] Luckily, the use of selumetinib in patients with NF-1 have shown efficacy in shrinking associated tumours and is linked to other positive clinical outcomes.[A193533] Selumetinib was approved by the FDA on April 10, 2020.[L49991] It was later approved by Health Canada on August 23, 2022.[L49986]
Synonyms
  • Selumetinibum
  • Selumetinib
  • Selumetinib sulfate
  • Sélumétinib
Brand NamesKoselugo
IndicationSelumetinib is indicated for the treatment of neurofibromatosis type 1 (NF1) in patients two years and older who have symptomatic, inoperable plexiform neurofibromas (PN).[A193611,L12852,L12969,L49986]
Categories
  • Antineoplastic Agents
  • Antineoplastic and Immunomodulating Agents
  • BCRP/ABCG2 Substrates
  • Cytochrome P-450 CYP1A2 Substrates
  • Cytochrome P-450 CYP2C19 Substrates
ATC-CodeL01EE04
CAS number606143-52-6

Drug Targets

NameTarget SequencePharmacological ActionActions
Dual specificity mitogen-activated protein kinase kinase 1MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRL...unknowninhibitor
Dual specificity mitogen-activated protein kinase kinase 2MLARRKPVLPALTINPTIAEGPSPTSEGASEANLVDLQKKLEELELDEQQ...unknowninhibitor
Cytochrome P450 2C19MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDV...unknownsubstrate
Cytochrome P450 3A4MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNI...unknownsubstrate
Cytochrome P450 2C9MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDI...unknownsubstrate
View More
Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID:21059682

Related Resource References

Resource NameReference
Pharos CHEMBL1614701
PubChem 10127622
ChEMBL CHEMBL1614701
ChEBI CHEBI:90227