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].

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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2D Structure
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Physico-chemical Properties
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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
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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)
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]