CX-4945 is an orally-available, ATP-competitive, pyridoquinoline-based inhibitor of CK2a with an IC50 potency of 1 nM and Ki of 0.38 nM. [1, 2] In a panel of 238 kinases at 500 nM, only 7 inhibited CK2 >90% [2] Treatment of BT474 and BxPC-3 cells with CX-4945 led to rapid dephosphorylation of CK2, Akt (S129), accompanied by reduction in phsophorylation at T308 and S473 of Akt. Since no reduction in PTEN phosphorylation at CK2's S370/S380, it is surmised that CX-4945 suppresses Pi3K/Akt signaling by directly blocking phosphorylation of Akt at Akt at S129 by CK2, rather than through activation of PTEN. [2]
Additionally, CX-4945 inhibits hypoxia-driven hypoxia inducible factor (HIF-1a) activity and prevents downregulation of pVHL and p53. CX-4945 also exerts a regulatory effect on the secretion of IL-6 in inflammatory breast cancer. [3]
CX-4945 may also be a potential sensitizer for resistant cells to conventional chemotherapeutic agents such as gemcitabine and cisplatin. [4]
Technical information:
| Chemical Formula: | C19H12ClN3O2 | |
| CAS #: | 1009820-21-6 | |
| Molecular Weight: | 349.77 | |
| Purity: | > 99% | |
| Appearance: | Yellow | |
| Chemical Name: | 5-(3-chlorophenylamino)benzo[c][2,6]naphthyridine-8-carboxylic acid | |
| Solubility: | Up to 100 mM in DMSO | |
| Synonyms: | CX-4945, CX 4945, CX4945, Silmitasertib |
Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage condition: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.
Reference:
| 1. | Pierre et al., Pre-clinical characterization of CX-4945, a potent and selective small molecule inhibitor of CK2 for the treatment of cancer. Mol. Cell. Biochem., 2011, 356, 37-43. Pubmed ID: 21755459 |
| 2. | Siddiqui-Jain et al., CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy. Cancer Res. 2010, 70, 10288-10298. Pubmed ID: 21159648 |
| 3. | Kim et al., Druggability of the CK2 inhibitor CX-4945 as an anticancer drug and beyond.. Arch. Pharm. Res. 2012, 35(8), 1293-1296. Pubmed ID: 22941473 |
| 4. | Zanin et al., Effects of the CK2 inhibitors CX-4945 and CX-5011 on drug-resistant cells.. PLosONE, 2012, 7(11), e49193. Pubmed ID: 21159648 |
Other Information:
Product Specification (pdf)
MSDS (pdf)
Certificate of Analysis is available upon request.
