3EW

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

Created:	2014-08-04
Last modified:	2021-03-12

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Chemical Details
Formal Charge	0
Atom Count	42
Chiral Atom Count	0
Bond Count	44
Aromatic Bond Count	16

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Chemical Component Summary
Name	5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide
Synonyms	Selumetinib
Systematic Name (OpenEye OEToolkits)	6-[(4-bromanyl-2-chloranyl-phenyl)amino]-7-fluoranyl-N-(2-hydroxyethyloxy)-3-methyl-benzimidazole-5-carboxamide
Formula	C₁₇ H₁₅ Br Cl F N₄ O₃
Molecular Weight	457.681
Type	NON-POLYMER

Chemical Descriptors
Type	Program	Version	Descriptor
SMILES	ACDLabs	12.01	Brc1ccc(c(Cl)c1)Nc2c(F)c3ncn(c3cc2C(=O)NOCCO)C
SMILES	CACTVS	3.385	Cn1cnc2c(F)c(Nc3ccc(Br)cc3Cl)c(cc12)C(=O)NOCCO
SMILES	OpenEye OEToolkits	1.9.2	Cn1cnc2c1cc(c(c2F)Nc3ccc(cc3Cl)Br)C(=O)NOCCO
Canonical SMILES	CACTVS	3.385	Cn1cnc2c(F)c(Nc3ccc(Br)cc3Cl)c(cc12)C(=O)NOCCO
Canonical SMILES	OpenEye OEToolkits	1.9.2	Cn1cnc2c1cc(c(c2F)Nc3ccc(cc3Cl)Br)C(=O)NOCCO
InChI	InChI	1.03	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	InChI	1.03	CYOHGALHFOKKQC-UHFFFAOYSA-N

Drug Info: DrugBank

DrugBank ID	DB11689
Name	Selumetinib
Groups	approved investigational
Description	Activation 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	Selumetinib sulfate Sélumétinib Selumetinibum Selumetinib
Brand Names	Koselugo
Indication	Selumetinib 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 Cytochrome P-450 CYP2C8 Substrates Cytochrome P-450 CYP2C9 Substrates Cytochrome P-450 CYP2E1 Substrates Cytochrome P-450 CYP3A Substrates Cytochrome P-450 CYP3A4 Substrates Cytochrome P-450 CYP3A5 Substrates Cytochrome P-450 Substrates Heterocyclic Compounds, Fused-Ring Kinase Inhibitor Mitogen-activated protein kinase (MEK) inhibitors Mitogen-Activated Protein Kinase Kinase 1 Inhibitors Mitogen-Activated Protein Kinase Kinase 2 Inhibitors P-glycoprotein substrates Protein Kinase Inhibitors Tyrosine Kinase Inhibitors UGT1A1 Substrates
ATC-Code	L01EE04
CAS number	606143-52-6

Drug Targets

Name	Target Sequence	Pharmacological Action	Actions
Dual specificity mitogen-activated protein kinase kinase 1	MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRL...	unknown	inhibitor
Dual specificity mitogen-activated protein kinase kinase 2	MLARRKPVLPALTINPTIAEGPSPTSEGASEANLVDLQKKLEELELDEQQ...	unknown	inhibitor
Cytochrome P450 2C19	MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDV...	unknown	substrate
Cytochrome P450 3A4	MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNI...	unknown	substrate
Cytochrome P450 2C9	MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDI...	unknown	substrate
Cytochrome P450 1A2	MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPL...	unknown	substrate
Cytochrome P450 2C8	MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDI...	unknown	substrate
Cytochrome P450 2E1	MSALGVTVALLVWAAFLLLVSMWRQVHSSWNLPPGPFPLPIIGNLFQLEL...	unknown	substrate
Cytochrome P450 3A5	MDLIPNLAVETWLLLAVSLVLLYLYGTRTHGLFKRLGIPGPTPLPLLGNV...	unknown	substrate
UDP-glucuronosyltransferase 1-1	MAVESQGGRPLVLGLLLCVLGPVVSHAGKILLIPVDGSHWLSMLGAIQQL...	unknown	substrate
UDP-glucuronosyltransferase 1-3	MATGLQVPLPWLATGLLLLLSVQPWAESGKVLVVPIDGSHWLSMREVLRE...	unknown
Serum albumin	MKWVTFISLLFLFSSAYSRGVFRRDAHKSEVAHRFKDLGEENFKALVLIA...	unknown	carrier
alpha1-acid glycoprotein	MALSWVLTVLSLLPLLEAQIPLCANLVPVPITNATLDQITGKWFYIASAF...	unknown	carrier
P-glycoprotein 1	MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLY...	unknown	substrate
ATP-binding cassette sub-family G member 2	MSSSNVEVFIPVSQGNTNGFPATASNDLKAFTEGAVLSFHNICYRVKLKS...	unknown	substrate
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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