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Formula | C19H12ClN3O2 |
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Molecular Weight | 349.77 | CAS No. | 1009820-21-6 | |
Solubility (25°C)* | In vitro | DMSO | 35 mg/mL (100.06 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | Silmitasertib (CX-4945) is a potent and selective inhibitor of CK2 (casein kinase 2) with IC50 of 1 nM in a cell-free assay, less potent to Flt3, Pim1 and CDK1 (inactive in cell-based assay). Silmitasertib induces autophagy and promotes apoptosis. Phase 1/2. | ||
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Targets |
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In vitro | CX-4945 is selective for CK2, as it only inhibits 7 of the 238 kinases by more than 90% at concentration of 0.5 μM, which is 500-fold greater than the IC50 of CK2. Although in cell-free systems CX-4945 inhibits FLT3, PIM1, and CDK1 with IC50 of 35 nM, 46 nM, and 56 nM, respectively, CX-4945 treatment at 10 μM is inactive against FLT3, PIM1, and CDK1 in cell-based functional assays. CX-4945 exhibits a broad spectrum of antiproliferative activity, and the breast cancer cell lines displays the widest range of sensitivity to CX-4945 with EC50 of 1.71-20.01 μM. The antiproliferative activity of CX-4945 correlates with CK2α mRNA and protein levels but not the CK2α' catalytic subunit, the regulatory CK2β subunit, and the PI3K/Akt or PTEN mutational status. CX-4945 inhibits PI3K/Akt signaling by directly blocking the phosphorylation of Akt at Serine 129 by CK2 rather than through activation of PTEN. CX-4945 treatment causes reduced phosphorylation of p21 (T145), increased levels of total p21 and p27, and induction of caspase 3/7 activity. CX-4945 treatment induces a G2/M cell-cycle arrest in BT-474 cells and a G1 arrest in BxPC-3 cells. CX-4945 inhibits HUVEC proliferation, migration, and tube formation with IC50 of 5.5 μM, 2 μM, and 4 μM, respectively. Under hypoxic conditions in BT-474 and BxPC-3 cells, CX-4945 treatment prevents downregulation of p53 and pVHL and reduces activation of HIF-1α transcription. [1] CX-4945 potently inhibits endogenous intracellular CK2 activity with IC50 of 0.1 μM in Jurkat cells. [2] |
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In vivo | Oral administration of CX-4945 at 25 mg/kg or 75 mg/kg twice daily displays potent antitumor activity in the BT-474 model, with TGI of 88% and 97%, respectively, and 2 of 9 animals in each group showing more than 50% reduction in tumor size compared with the initial tumor volume. In the BxPC-3 model, CX-4945 treatment at 75 mg/kg twice daily shows 93% TGI with 3 animals having no evidence of tumor remaining at the end of the treatment period. [1] In PC3 xenograft model, administration of CX-4945 at 25 mg/kg, 50 mg/kg, or 75 mg/kg causes tumor growth inhibition with TGI of 19%, 40%, and 86%, respectively. [2] |
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Features | First clinical inhibitor of CK2. |
Kinase Assay: |
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Cell Assay: |
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Animal Study: |
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Data from [Nat Commun, 2014, 5, 3393]
Data from [Cell Signal, 2014, 26(7), 1567-75]
Data from [Cell Signal, 2014, 26(7), 1567-75]
, , Oncotarget, 2015, 51: S659-S660
Body weight control via protein kinase CK2: diet-induced obesity counteracted by pharmacological targeting [ Metabolism, 2025, 162:156060] | PubMed: 39521118 |
CK2 activity is crucial for proper glucagon expression [ Diabetologia, 2024, 10.1007/s00125-024-06128-1] | PubMed: 38503901 |
Rutaecarpine alleviates inflammation and fibrosis by targeting CK2α in diabetic nephropathy [ Biomed Pharmacother, 2024, 180:117499] | PubMed: 39353318 |
Protein kinase CK2α is overexpressed in classical hodgkin lymphoma, regulates key signaling pathways, PD-L1 and may represent a new target for therapy [ Front Immunol, 2024, 15:1393485] | PubMed: 38807597 |
Sex-specific trisomic Dyrk1a-related skeletal phenotypes during development in a Down syndrome model [ Dis Model Mech, 2024, 17(9)dmm050914] | PubMed: 39136051 |
"Phosphoproteomic quantification based on phosphopeptide intensity or occupancy? An evaluation based on casein kinase 2 downstream effects" [ J Proteomics, 2024, 307:105269] | PubMed: 39098729 |
Mitochondrial ALDH2 improves ß-cell survival and function against doxorubicin-induced apoptosis by targeting CK2 signaling [ J Diabetes Investig, 2024, 15(6):684-692] | PubMed: 38713732 |
Sex specific emergence of trisomic Dyrk1a-related skeletal phenotypes in the development of a Down syndrome mouse model [ bioRxiv, 2024, 2024.05.24.595804] | PubMed: 38826419 |
Mcam stabilizes luminal progenitor breast cancer phenotypes via Ck2 control and Src/Akt/Stat3 attenuation [ bioRxiv, 2024, 2023.05.10.540211] | PubMed: 38562809 |
Reconstitution of BNIP3/NIX-mediated autophagy reveals two pathways and hierarchical flexibility of the initiation machinery [ bioRxiv, 2024, 2024.08.28.609967] | PubMed: 39253418 |
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