silmitasertib   Click here for help

GtoPdb Ligand ID: 8126

Synonyms: CX 4945 | CX-4945 | CX4945
PDB Ligand
Compound class: Synthetic organic
Comment: Silmitasertib (CX-4945) is a a potent and selective inhibitor of CK2 (casein kinase 2) [4-5]. CX-4945 is described in the same article as CX-5011 and CX-5279 [1].

SARS-CoV-2
Silmitasertib, via inhibition of CK2, was found to produce an in vitro antiviral effect (IC50 = 2.34 μM;) [2]. In conjunction with data supporting a physical interaction [3] and co-localization of CK2 with SARS-CoV-2 N protein, and evidence of potential role of CK2 in remodeling extracellular matrix upon infection [2], it can be hypothesised that the CK2 pathway is hijacked by SARS-CoV-2. Thus, it makes pharmacological sense that silmitasertib should be considered for investigation as an anti-SARS-CoV-2 therapeutic.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
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 5
Hydrogen bond donors 2
Rotatable bonds 3
Topological polar surface area 75.11
Molecular weight 349.06
XLogP 4.32
No. Lipinski's rules broken 0
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 Clc1cccc(c1)Nc1nc2cc(ccc2c2c1ccnc2)C(=O)O
Isomeric SMILES Clc1cccc(c1)Nc1nc2cc(ccc2c2c1ccnc2)C(=O)O
InChI InChI=1S/C19H12ClN3O2/c20-12-2-1-3-13(9-12)22-18-15-6-7-21-10-16(15)14-5-4-11(19(24)25)8-17(14)23-18/h1-10H,(H,22,23)(H,24,25)
InChI Key MUOKSQABCJCOPU-UHFFFAOYSA-N
Bioactivity Comments
CX-4945 induces apoptosis in cancer cells and inhibits molecular mechanisms underlying angoigenesis in HUVEC cells [5]. Low nanomolar IC50s are reported (in ascending value) for several other kinases including death-associated protein kinase 3 (DAPK3), fms-related tyrosine kinase 3 (FLT3), TANK-binding kinase 1 (TBK1), CDC-like kinase 3 (CLK3), homeodomain interacting protein kinase 3 (HIPK3), Pim-1 proto-oncogene (PIM1) and cyclin dependent kinase 1 (CDK1/cyclinB) [4].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
casein kinase 2, alpha 1 polypeptide subunit Primary target of this compound Hs Inhibitor Inhibition 9.0 pIC50 - 4
⤷ pIC50 9.0 (IC50 1x10-9 M) [4]
casein kinase 2, alpha prime polypeptide subunit Primary target of this compound Hs Inhibitor Inhibition 9.0 pIC50 - 4
⤷ pIC50 9.0 (IC50 1x10-9 M) [4]
death associated protein kinase 3 Hs Inhibitor Inhibition 7.8 pIC50 - 4
⤷ pIC50 7.8 (IC50 1.7x10-8 M) [4]
homeodomain interacting protein kinase 3 Hs Inhibitor Inhibition 7.3 pIC50 - 4
⤷ pIC50 7.3 (IC50 4.5x10-8 M) [4]
Pim-1 proto-oncogene, serine/threonine kinase Hs Inhibitor Inhibition 6.7 pIC50 - 1
⤷ pIC50 6.7 (IC50 2.16x10-7 M) [1]