selumetinib   

GtoPdb Ligand ID: 5665

Synonyms: ARRY-142886 | ARRY-886 | AZD6244 | Koselugo® | NSC 741O78
selumetinib is an approved drug (FDA (2020))
Compound class: Synthetic organic
Comment: Selumetinib is a selective, orally bioavailable MEK1/2 inhibitor [5].
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 4
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 88.41
Molecular weight 456
XLogP 3.7
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES OCCONC(=O)c1cc2n(C)cnc2c(c1Nc1ccc(cc1Cl)Br)F
Isomeric SMILES OCCONC(=O)c1cc2n(C)cnc2c(c1Nc1ccc(cc1Cl)Br)F
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)
InChI Key CYOHGALHFOKKQC-UHFFFAOYSA-N
References
1. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W et al.. (2002)
Mutations of the BRAF gene in human cancer.
Nature, 417 (6892): 949-54. [PMID:12068308]
2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011)
Comprehensive analysis of kinase inhibitor selectivity.
Nat. Biotechnol., 29 (11): 1046-51. [PMID:22037378]
3. Dombi E, Baldwin A, Marcus LJ, Fisher MJ, Weiss B, Kim A, Whitcomb P, Martin S, Aschbacher-Smith LE, Rizvi TA et al.. (2016)
Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas.
N. Engl. J. Med., 375 (26): 2550-2560. [PMID:28029918]
4. Gross AM, Wolters PL, Dombi E, Baldwin A, Whitcomb P, Fisher MJ, Weiss B, Kim A, Bornhorst M, Shah AC et al.. (2020)
Selumetinib in Children with Inoperable Plexiform Neurofibromas.
N. Engl. J. Med., 382 (15): 1430-1442. [PMID:32187457]
5. Huynh H, Soo KC, Chow PK, Tran E. (2007)
Targeted inhibition of the extracellular signal-regulated kinase kinase pathway with AZD6244 (ARRY-142886) in the treatment of hepatocellular carcinoma.
Mol. Cancer Ther., 6 (1): 138-46. [PMID:17237274]
6. Troiani T, Vecchione L, Martinelli E, Capasso A, Costantino S, Ciuffreda LP, Morgillo F, Vitagliano D, D'Aiuto E, De Palma R et al.. (2012)
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, 106 (10): 1648-59. [PMID:22569000]
7. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010)
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
Chem. Biol., 17 (11): 1241-9. [PMID:21095574]
8. Yeh TC, Marsh V, Bernat BA, Ballard J, Colwell H, Evans RJ, Parry J, Smith D, Brandhuber BJ, Gross S et al.. (2007)
Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor.
Clin. Cancer Res., 13 (5): 1576-83. [PMID:17332304]