Protein kinase CK2 is a tetrameric enzyme with two catalytic subunits and two regulatory subunits that constitutively actives serine/threonine protein kinase as a prototypical non-oncogene. CX-4945 Sodium is a selective inhibitor of CK2 catalytic subunits with an IC50 value of 1 nmol/L. Four-hour exposure to 5 and 10 μmol/L CX-4945 in BT-474 cells and BxPC-3 cells caused rapid dephosphorylation of CK2 phophorylation site, Akt (S129), and both canonical regulatory sites, Akt (T308) and Akt (S473). Treatment of BT-474 cells with 1-10 μmol/L CX-4945 for 24 hours induced a G2/M cell-cycle arrest, while the treatment of BxPC-3 cells led to G1/M arrest. Incubating HUVEC cells with 0.1-10 μmol/L CX-4945 led to rapid dephosphorylation of Akt (S129), Akt (T308) and Akt (S473) at 4 hours. Also in HUVEC cells, reduced phosphorylation at the CK2-phosphorylation sites on PTEN (S370/S380) was also observed after 24-hour exposure to 0.1-10 μmol/L CX-4945. CX-4945 inhibited HUVEC cell proliferation, migration, and tube formation with IC50 values of 5.5, 2, and 4 μmol/L at 72 hours, 24 hours and 18 hours, respectively. Treatment of BT-474 and BxPC-3 cells under hypoxic conditions with 5 μmol/L CX-4945 for 48 hours prevented the downregulation of p53 and pVHL. The activation of HIF-1α transcription in Hela cells under hypoxic versus normoxic conditions was also suppressed by 12.5 and 25 μmol/L CX-4945 48 hours after the treatment. In BT-474 xenograft mice, oral administration of 25 and 75 mg/kg CX-4945 twice a day for 31 days inhibited 88% and 97% tumor growth, respectively. In BxPC-3 mouse model, 75 mg/kg bid oral gavage of CX-4945 for 35 days resulted in 93% tumor growth inhibition[1].
作用机制
CX-4945 Sodium acts as an ATP-competitive inhibitor of both isoforms of CK2 catalytic subunits, CK2α and CK2α’, directly blocking the phosphorylation of Akt at Serine 129 in PI3K/Akt signaling pathway[1].
Silmitasertib sodium salt 细胞实验
Cell Line
Concentration
Treated Time
Description
References
U87MG cells
25 μM
6 h
To evaluate the effect of Silmitasertib on the stability of ECE1c protein, results showed that ECE1cK6R remained highly stable in the presence of Silmitasertib.
Cells. 2023 Feb 3;12(3):506.
Cal-27
10, 20, 40 µM
24, 48 h
Silmitasertib combined with DDP significantly reduced cell viability, showing a synergistic effect.
Drug Deliv. 2021 Dec;28(1):2480-2494.
UM1
10, 20, 40 µM
24, 48 h
Silmitasertib combined with DDP significantly reduced cell viability, showing a synergistic effect.
Drug Deliv. 2021 Dec;28(1):2480-2494.
HSC-3
10, 20, 40 µM
12 h
Silmitasertib induced the formation of vacuoles of different numbers and sizes in HSC-3 cells.
Drug Deliv. 2021 Dec;28(1):2480-2494.
HSC-4
10, 20, 40 µM
12 h
Silmitasertib induced the formation of vacuoles of different numbers and sizes in HSC-4 cells.
Drug Deliv. 2021 Dec;28(1):2480-2494.
OSC19
10 µM
12 h
Silmitasertib significantly inhibited invadopodia function and ECM degradation in OSC19 cells
Mol Cancer Res. 2019 Apr;17(4):987-1001.
UMSCC1
10 µM
12 h
Silmitasertib significantly inhibited invadopodia function and ECM degradation in UMSCC1 cells
Mol Cancer Res. 2019 Apr;17(4):987-1001.
MDA1586
10 µM
24 h
Silmitasertib significantly inhibited invadopodia function and ECM degradation in MDA1586 cells
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