The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
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
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Yung-Chi, C., & Prusoff, W. H. (1973) · Biochemical Pharmacology · doi:10.1016/0006-2952(73)90196-2 · Cited by 12,922
Principles of cancer therapy: oncogene and non-oncogene addiction
Luo, J., Solimini, N. L., & Elledge, S. J. (2009) · Cell · doi:10.1016/j.cell.2009.02.024 · Cited by 1,765
One‐thousand‐and‐one substrates of protein kinase CK2?
Meggio, F., & Pinna, L. A. (2003) · The FASEB Journal · doi:10.1096/fj.02-0473rev · Cited by 1,310
Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors
Jagtap, P., & Szabó, C. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1718 · Cited by 896
Siddiqui-Jain, A., Drygin, D., Streiner, N., Chua, P., Pierre, F., O'Brien, S. E., Bliesath, J., Omori, M., Huser, N., Ho, C., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1893 · Cited by 506
Self-citationCrystal structure of human protein kinase CK2: insights into basic properties of the CK2 holoenzyme
Niefind, K. (2001) · The EMBO Journal · doi:10.1093/emboj/20.19.5320 · Cited by 444
Addiction to protein kinase CK2: A common denominator of diverse cancer cells?
Ruzzene, M., & Pinna, L. A. (2010) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.07.018 · Cited by 352
Protein kinase CK2 phosphorylates and upregulates Akt/PKB
Di Maira, G., Salvi, M., Arrigoni, G., Marin, O., Sarno, S., Brustolon, F., Pinna, L. A., & Ruzzene, M. (2005) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401604 · Cited by 327
Duncan, J. S., & Litchfield, D. W. (2008) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2007.08.017 · Cited by 304
Zandomeni, R., Zandomeni, M. C., Shugar, D., & Weinmann, R. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)35799-x · Cited by 291
Cited by
Chen, H., Chen, F., Liu, N., Wang, X., & Gou, S. (2018) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2018.09.005 · Cited by 51
Basukala, O., Sarabia-Vega, V., & Banks, L. (2020) · Biological Chemistry · doi:10.1515/hsz-2019-0408 · Cited by 19
Metadata
- Authors
- Pierre, F., Chua, P. C., O’Brien, S. E., Siddiqui-Jain, A., Bourbon, P., Haddach, M., Michaux, J., Nagasawa, J., Schwaebe, M. K., Stefan, E., Vialettes, A., Whitten, J. P., Chen, T. K., Darjania, L., Stansfield, R., Anderes, K., Bliesath, J., Drygin, D., Ho, C., Omori, M., Proffitt, C., Streiner, N., Trent, K., Rice, W. G., & Ryckman, D. M.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-12-21
- Volume
- 54
- Issue
- 2
- Pages
- 635-654
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2033433713
- Cited by
- 296
- References
- 32
- FWCI
- 10.58
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: 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. https://app.cochat.ai/papers/10.1021/jm101251q
- The paper
- Pierre, F., Chua, P. C., O’Brien, S. E., Siddiqui-Jain, A., Bourbon, P., Haddach, M., Michaux, J., Nagasawa, J., Schwaebe, M. K., Stefan, E., Vialettes, A., Whitten, J. P., Chen, T. K., Darjania, L., Stansfield, R., Anderes, K., Bliesath, J., Drygin, D., Ho, C., . . . Ryckman, D. M. (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. Journal of Medicinal Chemistry. https://doi.org/10.1021/jm101251q
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
