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)
1. Battistutta R, Cozza G, Pierre F, Papinutto E, Lolli G, Sarno S, O'Brien SE, Siddiqui-Jain A, Haddach M, Anderes K et al.. (2011)
Unprecedented selectivity and structural determinants of a new class of protein kinase CK2 inhibitors in clinical trials for the treatment of cancer.
Biochemistry, 50 (39): 8478-88. [PMID:21870818]
2. Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV, Marrero MC, Polacco BJ, Melnyk JE, Ulferts S, Kaake RM. (2020)
The Global Phosphorylation Landscape of SARS-CoV-2 Infection.
Cell, Article Online Now. DOI: 10.1016/j.cell.2020.06.034
3. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL et al.. (2020)
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.
Nature, 583 (7816): 459-468. [PMID:32353859]
4. Pierre F, Chua PC, O'Brien SE, Siddiqui-Jain A, Bourbon P, Haddach M, Michaux J, Nagasawa J, Schwaebe MK, Stefan E et al.. (2011)
Discovery and SAR of 5-(3-chlorophenylamino)benzo[c][2,6]naphthyridine-8-carboxylic acid (CX-4945), the first clinical stage inhibitor of protein kinase CK2 for the treatment of cancer.
J Med Chem, 54 (2): 635-54. [PMID:21174434]
5. Siddiqui-Jain A, Drygin D, Streiner N, Chua P, Pierre F, O'Brien SE, Bliesath J, Omori M, Huser N, Ho C et al.. (2010)
CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy.
Cancer Res, 70 (24): 10288-98. [PMID:21159648]