Silmitasertib

SKU: orb1305875

Description

Silmitasertib (CX-4945) is a highly potent and orally bioavailable small molecule inhibitor of casein kinase 2 (CK2), demonstrating a Ki of 0.38 nM. It is widely used in cancer research, showing antitumor activity in both cellular assays and in vivo models across various cancer types.

Research Area

Cell Biology, Metabolism Research, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1009820-21-6
• MW: 349.77
• Purity: 99.90% (May vary between batches)
• Formula: C₁₉H₁₂ClN₃O₂
• SMILES: OC(=O)c1ccc2c(c1)nc(Nc1cccc(Cl)c1)c1ccncc21
• Target: Casein Kinase,Autophagy
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:17 mg/mL (48.6 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  CK2:1 nM (cell free)
• In Vivo:
  When administered orally in murine xenograft models, CX-4945 was well tolerated and demonstrated robust antitumor activity with concomitant reductions of the mechanism-based biomarker phospho-p21 (T145) . Mice bearing subcutaneous PC3 tumors were treated with CX-4945 (25 mg/kg, 50 mg/kg, and 75 mg/kg, po, bid). Tumor growth inhibition compared to vehicle-treated control, and a dose-responsive efficacy was observed. Last, CX-4945 was well tolerated in mice as assessed by minimal changes in body weight during the course of treatment compared to vehicle control .
• In Vitro:
  The antiproliferative activity of Silmitasertib (CX-4945) against cancer cells correlated with expression levels of the CK2α catalytic subunit. CX-4945 caused cell-cycle arrest and selectively induced apoptosis in cancer cells relative to normal cells. In models of angiogenesis, CX-4945 inhibited human umbilical vein endothelial cell migration, tube formation, and blocked CK2-dependent HIF-1α transcription in cancer cells . Adding CX-4945 after bortezomib treatment, prevented leukemic cells from engaging a functional UPR in order to buffer the bortezomib-mediated proteotoxic stress in ER lumen. Bortezomib/CX-4945 treatment inhibited NF-κB signaling in T-ALL cell lines and primary cells from T-ALL patients, but, in B-ALL cells the drug combination activated NF-κB p65 pro-apoptotic functions . CX-4945 was found to potently inhibit endogenous intracellular CK2 activity with an IC50 of 0.1 μM in Jurkat cells. CX-4945 induced dephosphorylation of Akt(S129) and a rapid dephosphorylation of the Akt substrate p21(T145). CX-4945 induced apoptosis in multiple cancer cell lines .
• Cell Research:
  Various cell lines were seeded at a density of 3000 cells per well 24 h prior to treatment, in appropriate media, and then treated with indicated concentrations of CK2 inhibitors. Suspension cells were seeded and treated on the same day. Following 4 days of incubation, 20 μL of Alamar Blue (10% of volume/well) was added and the cells were further incubated at 37 °C for 4-5 h. Fluorescence with excitation wavelength at 530-560 nm and emission wavelength at 590 nm was measured .
• Animal Research:
  Xenografts were initiated by subcutaneous injection of BxPC-3 cells into the right hind flank region of each mouse or BT-474 cells were injected into the mammary fat pad of mice implanted with estrogen pellets. When tumors reached a designated volume of 150-200 mm^3, animals were randomized and divided into groups of 9 to 10 mice per group. CX-4945 was administered by oral gavage twice daily at 25 or 75 mg/kg for 31 and 35 consecutive days for the BT-474 and BxPC-3 models, respectively. Tumor volumes and body weights were measured twice weekly. The length and width of the tumor were measured with calipers and the volume calculated using the following formula: tumor volume = (length × width^2)/2. Percent tumor growth inhibition (TGI) values were calculated on the final day of the study for CX-4945–treated compared to vehicle-treated mice and were calculated as 100 × {1 [(TreatedFinal day TreatedDay 1)/(ControlFinal day ControlDay 1)]}. The significance of the differences between the treated versus vehicle groups were determined using 1-way ANOVA .

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Silmitasertib, inhibit, Inhibitor, CK2, CX 4945, CX4945, CX-4945, Autophagy, Casein Kinase, CaseinKinase

Compound Identifiers

PubChem CID

24748573