Details of the Drug

General Information of Drug (ID: DMWE7B9)

• Drug Name: CX-4945
• Synonyms: 1009820-21-6; Silmitasertib; CX-4945; 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid; CX4945; CX-4945 (Silmitasertib); CX 4945; UNII-C6RWP0N0L2; 5-[(3-chlorophenyl)amino]-Benzo[c]-2,6-naphthyridine-8-carboxylic acid; 5-(3-chlorophenylamino)benzo[c][2,6]naphthyridine-8-carboxylic acid; C6RWP0N0L2; CHEMBL1230165; AK-82006; 5-[(3-Chlorophenyl)amino]benzo[c][2,6]naphthyridine-8-Carboxylic Acid; 5-((3-Chlorophenyl)amino)benzo-[c][2,6]naphthyridine-8-carboxylic acid; C19H12ClN3O2; W-204393

Indication

Disease Entry	ICD 11	Status	REF
Coronavirus infection	1D92	Phase 2	[1]
Cholangiocarcinoma	2C12.10	Phase 1/2	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[3], [4]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 349.8
  Topological Polar Surface Area (xlogp); 4.4
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C19H12ClN3O2
  IUPAC Name: 5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid
  Canonical SMILES: C1=CC(=CC(=C1)Cl)NC2=NC3=C(C=CC(=C3)C(=O)O)C4=C2C=CN=C4
  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)
  InChIKey: MUOKSQABCJCOPU-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 24748573
  CAS Number: 1009820-21-6
  TTD ID: D09JEJ
  VARIDT ID: DR00803

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Casein kinase II (CSNK2)	TTZ5NI7	NOUNIPROTAC	Modulator	[5]
Casein kinase II alpha (CSNK2A1)	TTER6YH	CSK21_HUMAN	Inhibitor	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Coronavirus infection
• ICD Disease Classification: 1D92

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Casein kinase II alpha (CSNK2A1)	DTT	CSNK2A1	6.82E-04	0.29	2.43

References

• [1] ClinicalTrials.gov (NCT04668209) Silmitasertib (CX-4945) in Patients With Severe Coronavirus Disease 2019 (COVID-19) (CX4945). U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8126).
• [4] ClinicalTrials.gov (NCT01199718) Study of CX-4945 in Patients With Relapsed or Refractory Multiple Myeloma. U.S. National Institutes of Health.
• [5] CX-4945, a selective inhibitor of casein kinase-2 (CK2), exhibits anti-tumor activity in hematologic malignancies including enhanced activity in chronic lymphocytic leukemia when combined with fludarabine and inhibitors of the B-cell receptor pathway. Leukemia. 2013 Oct;27(10):2094-6.
• [6] Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A. J Med Chem. 1996 Dec 20;39(26):5215-27.
• [7] Structural insight into human CK2alpha in complex with the potent inhibitor ellagic acid. Bioorg Med Chem Lett. 2009 Jun 1;19(11):2920-3.
• [8] 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9.
• [9] Structure and Property Based Design of Pyrazolo[1,5-a]pyrimidine Inhibitors of CK2 Kinase with Activity in Vivo. ACS Med Chem Lett. 2013 Jul 3;4(8):800-5.
• [10] Adenosine-5'-carboxylic acid peptidyl derivatives as inhibitors of protein kinases. Bioorg Med Chem Lett. 1999 May 17;9(10):1447-52.
• [11] CK2alpha and CK2alpha' subunits differ in their sensitivity to 4,5,6,7-tetrabromo- and 4,5,6,7-tetraiodo-1H-benzimidazole derivatives. Eur J Med Chem. 2012 Jan;47(1):345-50.
• [12] Synergistic interactions of the anti-casein kinase 2 CIGB-300 peptide and chemotherapeutic agents in lung and cervical preclinical cancer models. Mol Clin Oncol. 2014 Nov;2(6):935-944.
• [13] Tetrabromocinnamic acid (TBCA) and related compounds represent a new class of specific protein kinase CK2 inhibitors. Chembiochem. 2007 Jan 2;8(1):129-39.