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Purity: ≥98%
Silmitasertib (CX-4945; CX4945; CX 4945) is a potent, selective, orally bioavailable small-molecule inhibitor of CK2 (casein kinase 2) with potential anticancer activity. It inhibits CK2 with an IC50 of 1 nM in a cell-free assay, and shows less potency againt Flt3, Pim1 and CDK1 (inactive in cell-based assay). CX-4945 selectively binds to and inhibits the enzyme casein kinase II (CK2), which may lead to an inhibition of cellular proliferation. CK2 is a protein kinase overexpressed in a variety of cancer cell types and is correlated with malignant transformation, tumor growth and survival.
| ln Vitro |
Cell-cycle arrest and selective apoptosis in cancer cells as compared to normal cells are caused by silmitasertib (CX-4945), which also attenuates PI3K/Akt signaling. The antiproliferative activity of silmitasertib (CX-4945) is correlated with the expression levels of the CK2α catalytic subunit. In order to buffer the PS-341-mediated proteotoxic stress in the ER lumen, leukemic cells cannot engage a functional UPR. Silmitasertib (CX-4945) with PS-341 therapy reduces pro-survival ER chaperon BIP/Grp78 expression[2]. Activation of the CK2-mediated PI3K/Akt/mTOR signaling pathways is suppressed and cytotoxicity and apoptosis are induced in hematological malignancies by silmitasertib (CX-4945) via downregulating CK2 expression[3].
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| ln Vivo |
In murine xenograft models, silmitasertib (CX-4945) (25 or 75 mg/kg, po) is well tolerated and has shown strong anticancer activity with simultaneous decreases in the mechanism-based biomarker phospho-p21 (T145)[1].
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| Additional Infomation |
Silmitasertib is under investigation in clinical trial NCT03904862 (Testing the Safety and Tolerability of CX-4945 in Patients With Recurrent Medulloblastoma Who May or May Not Have Surgery).
Silmitasertib is an orally bioavailable small-molecule inhibitor of the enzyme casein kinase II (CK2), with potential antineoplastic, anti-viral and immunomodulatory activities. Upon oral administration, silmitasertib selectively binds to and inhibits the activity of CK2. This may inhibit proliferation of CK2-expressing tumor cells, and may also inhibit the replication of severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). In addition, this may restore normal host cell cytokine regulation, prevent cytokine storm and suppress the hyperactivation of the innate immune system. CK2, a protein kinase often overexpressed in a variety of cancer cell types, appears to be correlated with malignant transformation, tumor growth and survival. CK2 regulates a diverse array of pro-survival cellular processes including epidermal growth factor receptor (EGFR) signaling, PI3K/AKT/mTOR signaling, hedgehog (Hh) signaling, Hsp90 machinery, hypoxia, and interleukin (IL)-6 expression. CK2 also regulates the activity of XRCC1 and MDC1, two mediator/adaptor proteins that are essential for DNA repair. CK2 is upregulated by SARS-COV-2 and is associated with SARS-COV-2 viral replication and the development of cytokine storm. |
| Molecular Formula |
C19H12CLN3O2
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| Molecular Weight |
349.77
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| Exact Mass |
349.061
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| CAS # |
1009820-21-6
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| Related CAS # |
Silmitasertib sodium salt;1309357-15-0
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| PubChem CID |
24748573
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| Appearance |
Yellow to orange solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
568.5±50.0 °C at 760 mmHg
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| Flash Point |
297.6±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.789
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| LogP |
3.29
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
25
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| Complexity |
491
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MUOKSQABCJCOPU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H12ClN3O2/c20-12-2-1-3-13(9-12)22-18-15-6-7-21-10-16(15)14-5-4-11(19(24)25)8-17(14)23-18/h1-10H,(H,22,23)(H,24,25)
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| Chemical Name |
5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (5.95 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (5.95 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8590 mL | 14.2951 mL | 28.5902 mL | |
| 5 mM | 0.5718 mL | 2.8590 mL | 5.7180 mL | |
| 10 mM | 0.2859 mL | 1.4295 mL | 2.8590 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04668209 | Terminated Has Results | Drug: Silmitasertib | Coronavirus | University of Arizona | January 21, 2021 | Phase 2 |
| NCT05817708 | Completed | Drug: CX-4945 | COVID-19 | Senhwa Biosciences, Inc. | November 7, 2022 | Phase 1 |
| NCT06202521 | Not yet recruiting | Drug: CX-4945 (SARS-CoV-2 domain) Drug: Placebo (SARS-CoV-2 domain) |
Community-acquired Pneumonia | Senhwa Biosciences, Inc. | March 2024 | Phase 2 |
| NCT03897036 | Active, not recruiting | Drug: CX-4945 | Carcinoma, Basal Cell | Senhwa Biosciences, Inc. | April 1, 2019 | Phase 1 |
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