Title: 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.

Abstract: Herein we chronicle the discovery of CX-4945 (25n), a first-in-class, orally bioavailable ATP-competitive inhibitor of protein kinase CK2 in clinical trials for cancer. CK2 has long been considered a prime cancer drug target because of the roles of deregulated and overexpressed CK2 in cancer-promoting prosurvival and antiapoptotic pathways. These biological properties as well as the suitability of CK2's small ATP binding site for the design of selective inhibitors, led us to fashion novel therapeutic agents for cancer. The optimization leading to 25n (K(i) = 0.38 nM) was guided by molecular modeling, suggesting a strong binding of 25n resulting from a combination of hydrophobic interactions, an ionic bridge with Lys68, and hydrogen bonding with the hinge region. 25n was found to be highly selective, orally bioavailable across species (20-51%) and efficacious in xenograft models. The discovery of 25n will allow the therapeutic targeting of CK2 in humans for the first time.
(PMID: 21174434)

Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Putative Target:

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: Cyclin-dependent kinase 1
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: Cyclin-dependent kinase 1
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: Cyclin-dependent kinase 1
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: Cyclin-dependent kinase 1
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: G2/mitotic-specific cyclin-B1
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: G2/mitotic-specific cyclin-B1
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: G2/mitotic-specific cyclin-B1
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: G2/mitotic-specific cyclin-B1
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: G2/mitotic-specific cyclin-B2
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: G2/mitotic-specific cyclin-B2
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: G2/mitotic-specific cyclin-B2
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: G2/mitotic-specific cyclin-B2
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: G2/mitotic-specific cyclin-B3
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: G2/mitotic-specific cyclin-B3
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: G2/mitotic-specific cyclin-B3
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Target ID: 104709
Target Type: PROTEIN COMPLEX
Pref Name: Cyclin-dependent kinase 1/cyclin B
Description: G2/mitotic-specific cyclin-B3
Organism: Homo sapiens
Tax ID: 9606
Confidence: Homologous protein complex subunits assigned
Relationship Type: Homologous protein target assigned
ChEMBL target type: Target is a defined protein complex, consisting of multiple subunits

ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature