compound 24 [PMID: 35286090]   Click here for help

GtoPdb Ligand ID: 12005

Compound class: Synthetic organic
Comment: This compound is reported as an inhibitor of kinesin family member 18A (KIF18A; Q8NI77) [1]. Compound 24 binds at the interface of KIF18A and tubulin. KIF18A is a molecular target for the development of therapeutics for chromosomally unstable cancers. Inhibiting KIF18A function drives mitotic arrest and cell death. Compound 24 shares some structural similarity with the clinical stage KIF18A inhibitor AMG650.
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 CDK toolkit. 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 9
Hydrogen bond donors 3
Rotatable bonds 10
Topological polar surface area 141.44
Molecular weight 574.23
XLogP 5.06
No. Lipinski's rules broken 1
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.

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Canonical SMILES O=C(c1ccc(cc1N1CCC2(CC1)CC2)NS(=O)(=O)C1(C)CC1)Nc1cccc(c1)S(=O)(=O)NC(C)(C)C
Isomeric SMILES CC(C)(C)NS(=O)(=O)c1cc(NC(=O)c2c(cc(NS(=O)(=O)C3(C)CC3)cc2)N2CCC3(CC3)CC2)ccc1
InChI InChI=1S/C28H38N4O5S2/c1-26(2,3)31-38(34,35)22-7-5-6-20(18-22)29-25(33)23-9-8-21(30-39(36,37)27(4)10-11-27)19-24(23)32-16-14-28(12-13-28)15-17-32/h5-9,18-19,30-31H,10-17H2,1-4H3,(H,29,33)
InChI Key MZGYQJDGUVDYIK-UHFFFAOYSA-N
References
1. Tamayo NA, Bourbeau MP, Allen JR, Ashton KS, Chen JJ, Kaller MR, Nguyen TT, Nishimura N, Pettus LH, Walton M et al.. (2022)
Targeting the Mitotic Kinesin KIF18A in Chromosomally Unstable Cancers: Hit Optimization Toward an In Vivo Chemical Probe.
J Med Chem, 65 (6): 4972-4990. [PMID:35286090]