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
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)
No information available.
Summary of Clinical Use
Selumetinib (administered clinically as the hydrogen sulfate) is being investigated for the treatment of various types of cancer, such as non-small cell lung cancer (NSCLC) and AIDS-related Kaposi's sarcoma. Click here to view's list of registered selumetinib trials.
In April 2015, the US FDA granted selumetinib orphan drug status as a treatment for uveal melanoma.
The first FDA approval of selumetinib was granted in April 2020, as a therapy for pediatric patients (≥2 years of age), who have symptomatic neurofibromatosis type 1 (NF1)-associated, inoperable plexiform neurofibromas (PN) [3].
Mechanism Of Action and Pharmacodynamic Effects
Selumetinib inhibits the MAPK kinases, MEK1 and MEK2 [6]. These kinases act in the MAPK/ERK pathway, downstream of BRAF and KRAS, two additional kinases which have been shown to carry activating mutations in some cancers [1]. Inhibition of MEK1/2 reduces abberant signalling in the growth factor-responsive MAPK/ERK signalling pathway in such cancer cells, and thereby reduces tumour growth.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01362803 AZD6244 Hydrogen Sulfate for Children With Nervous System Tumors Phase 1/Phase 2 Interventional National Institutes of Health Clinical Center (CC) Selumetinib was approved as the first oral monotherapy for pediatric patients with NF1-related plexiform neurofibromas. Regulatory approval was based on results from the SPRINT (NCT01362803) clinical trial which showed that selumetinib induced durable tumour shrinkage and clinical benefit in these patients. 4