CX-4945 (Silmitasertib) is the first orally available small molecule inhibitor of protein CK2 in clinical trials for cancer. CX-4945 (Silmitasertib) selectively binds to and inhibits the enzyme casein kinase II (CK2). Protein kinase CK2 (CK2) is involved in a variety of roles essential to the maintenance of cellular homeostasis. CK2 promotes signaling in the Akt pathway and CX-4945 suppresses the phosphorylation of Akt as well as other key downstream mediators of the pathway such as p21. CX-4945 has been reported to show broad spectrum anti-proliferative activity in multiple cancer cell lines. CX-4945 induced apoptosis and caused cell cycle arrest in cancer cells in vitro. CX-4945 exhibited a dose-dependent antitumor activity in a xenograft model of PC3 prostate cancer model and was well tolerated. In vivo time-dependent reduction in the phosphorylation of the biomarker p21 at T145 was observed by immunohistochemistry.
Sci Rep. 2017 Dec 14;7(1):17569.
CK2 modulates adipocyte insulinsignaling and is up-regulated in human obesity
Silmitasertib (CX-4945) purchased from AbMole
UNIVERSITA’ DEGLI STUDI DI PADOVA. 2017.
UNDERSTANDING THE MECHANISMS OF ADIPOSE TISSUE EXPANSION IN MULTIPLE SYMMETRIC LIPOMATOSIS AND OBESITY
Silmitasertib (CX-4945) purchased from AbMole
Biochim Biophys Acta. 2015 Jul;1853(7):1693-701.
Protein kinase CK2 potentiates translation efficiency by phosphorylating eIF3j at Ser127.
Silmitasertib (CX-4945) purchased from AbMole
Biomed Res Int. 2015;601543.
Phosphorylation, Signaling, and Cancer: Targets and Targeting.
Silmitasertib (CX-4945) purchased from AbMole
Growth Factors. 2015 Sep 04;259-266.
Effects of CK2 inhibition in cultured fibroblasts from Type 1 Diabetic patients with or without nephropathy.
Silmitasertib (CX-4945) purchased from AbMole
Cell Experiment | |
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Cell lines | BT-474 (breast) or BxPC-3 (pancreatic) cancer or HUVEC cells |
Preparation method | A 5 mmol/L stock solution in dimethyl sulfoxide was prepared and stored at - 70 ℃. The drug was diluted directly into growth media immediately prior to use.Various cell lines were seeded at a density of 3,000 cells per well 24 hours prior to treatment, in appropriate media, and then treated with indicated concentrations of CX-4945. Suspensions cells were seeded and treated on the same day.Following 4 days of incubation, Alamar Blue (20 mL, 10% of volume per well) was added and the cells were further incubated at 37 C for 4–5 hours. Fluorescence with excitation wavelength at 530–560 nm and emission wavelength at 590 nm was measured. |
Concentrations | 0, 0.1, 1.0, 5.0, 10 µM |
Incubation time | 24 h |
Animal Experiment | |
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Animal models | Female immunocompromised mice CrTac:Ncr-Foxn1nu (5–7 weeks old) BT474 or BxPC-3 cells Xenografts |
Formulation | Solubilized in DMSO and diluted with PBS containing 10% dimethylacetamide (Sigma-Aldrich) and 6% Solutol (Sigma-Aldrich). |
Dosages | twice daily at 25 or 75 mg/kg for 31 and 35 consecutive days |
Administration | oral gavage |
Molecular Weight | 349.77 |
Formula | C19H12ClN3O2 |
CAS Number | 1009820-21-6 |
Solubility (25°C) | DMSO ≥ 46 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[3] Ferguson et al. FEBS Lett. Structural basis of CX-4945 binding to human protein kinase CK2.
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ON 108600
ON 108600 is an inhibitor of CK2 (Casein Kinase2)/TNIK/DYRK1 with IC50 values of 0.016 μm/0.007 μM, 0.028 μM, 0.05 μM/0.005 μM, and 0.005 μM for DYRK1A/DYRKB, DYRK2, CK2α1/CK2α2, and TNIK, respectively. 0.005 μM. It has anti-tumor activity. |
(R)-DRF053 dihydrochloride
(R)-DRF053 dihydrochloride is a potent inhibitor of casein kinase 1 (CK1), CDK1/cyclin B, and CDK5/p25, with IC50s of 14 nM, 220 nM, and 80 nM, respectively.(R)-DRF053 dihydrochloride prevented the production of CK1-dependent amyloid-β in cellular models. In addition, (R)-DRF053 dihydrochloride prevented the production of CK1-dependent amyloid-β in cell models. |
Casein kinase 1δ-IN-5
Casein kinase 1δ-IN-5 is a potent and selective protein kinase CK-1δ inhibitor with an IC50 of 47 nM, which has neuroprotective and anti-inflammatory properties in vitro. It has neuroprotective and anti-inflammatory properties in vitro. It can be used in studies related to neurodegenerative diseases. |
CK2-IN-1
CK2-IN-1 is a CK2 inhibitor with an IC50 value of 150 nM. |
SR-1277
SR-1277 is a potent, selective and ATP-competitive CK1δ/ε inhibitor with IC50 values of 49 nM and 260 nM, respectively.In addition, SR-1277 inhibits FLT3, CDK4/cyclin D1, CDK6/cyclin D3, and CDK9/cyclin K with IC50 values of 305 nM, 1340 nM, 311 nM, and 109 nM, respectively. 1340 nM, 311 nM and 109 nM, respectively, and can be used in cancer research. |
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