zunsemetinib   Click here for help

GtoPdb Ligand ID: 11681

Synonyms: ATI-450 | ATI450 | CDD-450 | CDD450
Compound class: Synthetic organic
Comment: We obtained the chemical structure for zunsemetinib from WHO Proposed list 125 of July 2021. This mapped to PubChem CID 86291496. The compound is claimed in Confluence Life Sciences' patent US9115089B2 as kinase inhibitor with potential to treat p38 kinase-mediated diseases [2]. Confluence Life Sciences is a subsidiary of Aclaris Therapeutics. We speculate that zunsemetinib is the MAPK-activated protein kinase 2 (MK2) inhibitor ATI-450 (formerly CDD-450 [3]), that is included on Aclaris' pipeline page. Phase 1 safety and tolerability of ATI-450 were reported in June 2021 [1]. This article described ATI-450 as an inhibitor of p38α/MK2 pathway-mediated inflammatory signalling, but discloses only a partial chemical structure in a supplementary figure. The same incomplete chemical structure appears in [3]. ATI-450 binds with high affinity to the interface of the p38MAPK-MK2 complex and selectively inhibits p38MAPK-catalysed phosphorylation of MK2 which stabilises the inactive conformation of MK2, and subsequently reduces inflammatory cytokine levels [3].

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2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 102.5
Molecular weight 513.14
XLogP 3.28
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Fc1cnc(c(c1)F)COc1cc(C)n(c(=O)c1Cl)c1cc(ncc1C)c1ccnc(n1)C(O)(C)C
Isomeric SMILES Cc1cc(OCc2ncc(F)cc2F)c(Cl)c(=O)n1c1cc(ncc1C)c1nc(ncc1)C(C)(C)O
InChI InChI=1S/C25H22ClF2N5O3/c1-13-10-30-18(17-5-6-29-24(32-17)25(3,4)35)9-20(13)33-14(2)7-21(22(26)23(33)34)36-12-19-16(28)8-15(27)11-31-19/h5-11,35H,12H2,1-4H3
InChI Key FQPQMJULRZINPV-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
3-chloro-4-[(3,5-difluoropyridin-2-yl)methoxy]-1-[2-[2-(2-hydroxypropan-2-yl)pyrimidin-4-yl]-5-methylpyridin-4-yl]-6-methylpyridin-2-one
International Nonproprietary Names Click here for help
INN number INN
11983 zunsemetinib
Synonyms Click here for help
ATI-450 | ATI450 | CDD-450 | CDD450
Database Links Click here for help
BindingDB Ligand 175242
CAS Registry No. 1640282-42-3 (source: WHO INN record)
ChEMBL Ligand CHEMBL3704901
GtoPdb PubChem SID 442878707
PubChem CID 86291496
Search Google for chemical match using the InChIKey FQPQMJULRZINPV-UHFFFAOYSA-N
Search Google for chemicals with the same backbone FQPQMJULRZINPV
Search PubMed clinical trials zunsemetinib
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Search PubMed titles/abstracts zunsemetinib
UniChem Compound Search for chemical match using the InChIKey FQPQMJULRZINPV-UHFFFAOYSA-N
UniChem Connectivity Search for chemical match using the InChIKey FQPQMJULRZINPV-UHFFFAOYSA-N

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MedChemExpress
(R)-Zunsemetinib (links to external site)
Cat. No. HY-139553A
Zunsemetinib (links to external site)
Cat. No. HY-139553