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Chemical Structure| 1009820-21-6 Chemical Structure| 1009820-21-6

Structure of Silmitasertib
CAS No.: 1009820-21-6

Chemical Structure| 1009820-21-6

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Silmitasertib is a selective CK2 inhibitor with high affinity for CK2, with IC50 values of 1 nM for both CK2α and CK2α'. Silmitasertib exhibits antitumor and anti-inflammatory effects and is mainly used in research on cancer and inflammation-related diseases.

Synonyms: CX-4945

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Product Citations

Product Citations

Marlhoux, Léna ; Arnaud, Alexandre ; Hervieu, Céline ; Makulyte, Gabriela ; Martinasso, Charlotte ; Mularoni, Angélique , et al.

Abstract: Casein kinase 2 (CK2) has emerged as a promising therapeutic target across a broad spectrum of malignancies, including pediatric and orphan cancers. The identification of a ligandable allosteric αD pocket on the CK2α subunit has enabled the development of bivalent inhibitors, which bind simultaneously to both the adenosine triphosphate (ATP) site and the allosteric pocket. Here, we report the discovery and pharmacological characterization of KDX1381, a structure-guided bivalent CK2α inhibitor with low-nanomolar potency and high selectivity, confirmed by cocrystal structures. In mice, KDX1381 suppressed CK2-driven tumor growth as a monotherapy and enhanced therapeutic efficacy when combined with vascular endothelial growth factor receptor (VEGFR) inhibitors or DNA-damaging agents in hepatocellular carcinoma and glioma models. These findings support bivalent CK2α inhibition as a differentiated therapeutic strategy with broad applicability in CK2-dependent cancers.

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Product Details of Silmitasertib

CAS No. :1009820-21-6
Formula : C19H12ClN3O2
M.W : 349.77
SMILES Code : O=C(C1=CC=C2C(N=C(NC3=CC=CC(Cl)=C3)C4=C2C=NC=C4)=C1)O
Synonyms :
CX-4945
MDL No. :MFCD13184796
InChI Key :MUOKSQABCJCOPU-UHFFFAOYSA-N
Pubchem ID :24748573

Safety of Silmitasertib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Related Pathways of Silmitasertib

DNA
Hedgehog

Isoform Comparison

Biological Activity

Target
  • CK2

    CK2, IC50:1 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
U87MG 25 μM 6 h To study the effect of CK2 inhibitor on ECE1c stability, results showed that ECE1cK6R exhibited enhanced stability both in the presence and absence of silmitasertib. PMC9914402
T98G 25 μM 6 h To study the effect of CK2 inhibitor on ECE1c stability, results showed that ECE1cK6R exhibited enhanced stability both in the presence and absence of silmitasertib. PMC9914402
U251 25 μM 6 h To study the effect of CK2 inhibitor on ECE1c stability, results showed that ECE1cK6R exhibited enhanced stability both in the presence and absence of silmitasertib. PMC9914402
MCF-7 1 μM 24 h To evaluate the effect of Silmitasertib on cell viability. Results showed a significant reduction in cell viability. PMC6530875
HCT-116 2 μM 48 h To assess the impact of Silmitasertib on apoptosis. Results indicated an increase in apoptotic cells. PMC6530875
H1299 cells 37 μM 1 h To investigate the effect of Silmitasertib on N protein LLPS, results showed that Silmitasertib had no detectable effect on N protein LLPS. PMC8035206
HNSCC cells (OSC19, UMSCC1, MDA1586) 0.5-10 µM 12-24 h To evaluate the effect of Silmitasertib on HNSCC cell invasion, results showed that Silmitasertib significantly reduced extracellular matrix (ECM) degradation and invadopodia formation. PMC6445698
PDX cells (WVUSCC-AR2, WVUSCC-AR5) 0.5-10 µM 24 h To evaluate the effect of Silmitasertib on PDX cell invasion, results showed that Silmitasertib significantly reduced extracellular matrix (ECM) degradation and invadopodia formation. PMC6445698
Cal-27 10, 20, 40 µM 24, 48 h To test the effect of Silmitasertib combined with DDP treatment on the viability of Cal-27 cells, the results showed that the combined treatment significantly reduced cell viability. PMC8592591
UM1 10, 20, 40 µM 24, 48 h To test the effect of Silmitasertib combined with DDP treatment on the viability of UM1 cells, the results showed that the combined treatment significantly reduced cell viability. PMC8592591
HSC-3 10, 20, 40 µM 12 h To observe the effect of Silmitasertib on macropinocytosis in HSC-3 cells, the results showed that Silmitasertib induced cell vacuolation. PMC8592591
HSC-4 10, 20, 40 µM 12 h To observe the effect of Silmitasertib on macropinocytosis in HSC-4 cells, the results showed that Silmitasertib induced cell vacuolation. PMC8592591

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
BALB/c nude mice ovarian cancer xenograft model oral 60 mg/kg twice daily, until the end of the experiment Silmitasertib significantly inhibited tumor growth PMC11743126
Mice Xenograft model Oral 50 mg/kg Once daily for 21 days To determine the efficacy of Silmitasertib in reducing tumor growth. Results showed a significant reduction in tumor volume. PMC6530875
Mice HNSCC orthotopic tongue tumor model Oral 50 mg/kg Twice daily for three weeks To evaluate the effect of Silmitasertib on HNSCC orthotopic tongue tumor invasion, results showed that Silmitasertib significantly reduced tumor invasion and perineural invasion. PMC6445698
Nude mice Cal-27 xenograft model Peritumoral injection 60 mg/kg Once every 5 days for 4 weeks To verify the tumor suppressive effect of Silmitasertib combined with DDP in vivo, the results showed that the combined treatment significantly inhibited tumor growth. PMC8592591

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00891280 Advanced Solid Tumors ... More >> Breast Cancer Inflammatory Breast Cancer Castleman's Disease Multiple Myeloma Less << Phase 1 Unknown December 2011 United States, Arizona ... More >> Mayo Clinic Arizona Recruiting Scottsdale, Arizona, United States, 85259 Contact: Clinical Trials Office Mayo Clinic Cancer Center    507-538-7623       Principal Investigator: Donald Northfelt, MD          United States, Colorado Front Range Cancer Specialists Recruiting Fort Collins, Colorado, United States, 80528 Contact: P. Zeller    970-212-7609       Principal Investigator: Robert F Marschke, MD          Front Range Cancer Specialists Recruiting Loveland, Colorado, United States, 80528 Contact: Pat Zeller    970-212-7609       Principal Investigator: R. McFarland, MD          United States, Texas U T M D Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact: R. Alvarez, MD       ralvarez@mdanderson.org    Principal Investigator: R. Alvarez, MD Less <<
NCT03571438 Kidney Cancer Not Applicable Recruiting September 30, 2024 France ... More >> Grenoble Alps Hospital Recruiting Grenoble, France, 38043 Contact: Jean-Luc Descotes, PU-PH Less <<
NCT02128282 Cholangiocarcinoma Phase 1 Phase 2 Recruiting November 2021 United States, Arizona ... More >> Mayo Clinic Recruiting Scottsdale, Arizona, United States, 85259-5499 Contact: Mayo Clinic Clinical Trials Office    855-776-0015       Principal Investigator: Mitesh Borad, M.D.          United States, Colorado University of Colorado- Denver Recruiting Aurora, Colorado, United States, 80045 Contact: Amy Szilard    720-848-0702    Amy.Szilard@ucdenver.edu    Principal Investigator: Sarah (Lindsey) Davis, MD          United States, Florida Mayo Clinic Recruiting Jacksonville, Florida, United States, 32224 Contact: Mayo Clinic Clinical Trials Office    855-776-0015       Principal Investigator: Kabir Mody, MD          United States, Minnesota Mayo Clinic Recruiting Rochester, Minnesota, United States, 55905 Contact: Mayo Clinic Clinical Trials Office    855-776-0015       Principal Investigator: Joleen Hubbard, MD          United States, Texas Texas Oncology - Baylor Charles A. Sammons Cancer Center Recruiting Dallas, Texas, United States, 75246 Contact: Tammy Carmical, RN    214-370-1937    tammy.carmical@usoncology.com    Principal Investigator: Carlos Becerra, M.D.          Texas Oncology-Tyler Recruiting Tyler, Texas, United States, 75702 Contact: Karen Poe, RN    903-579-9869    karen.poe@usoncology.com    Principal Investigator: Donald A Richards, M.D.          Korea, Republic of Asan Medical Center Recruiting Seoul, Songpa-gu, Korea, Republic of, 138-736 Contact: Heung-Moon Chang, MD    82-3010-3219 ext 3210    changhm@amc.seoul.kr    Contact: Seok kyung Jeong    82-2-3010-5634    jsk0213@amc.seoul.kr    Samsung Medical Center Recruiting Seoul, Korea, Republic of Contact: Eunyou Lee    82-2-3410-0955    ley0709@samsung.com    Principal Investigator: Joon Oh Park, MD          Seoul National University Hospital Recruiting Seoul, Korea, Republic of Contact: Myoungsun Choi    82-2-2072-7612    iamyou3@hanmail.net    Principal Investigator: Do-Youn Oh, MD          Severance Hospital, Yonsei University Health System Recruiting Seoul, Korea, Republic of Contact: So Young Hwang    82-2-2228-8180    syhwang@yuhs.ac    Principal Investigator: Sun Young Rha, MD          Taiwan China Medical University Hospital Recruiting Taichung City, Taiwan Contact: Pei-Chen Hsu    +886-4-2205-2121    peggyshiu0807@gmail.com    Principal Investigator: Li-Yuan Bai, M.D. Less <<
NCT01199718 Multiple Myeloma PHASE1 UNKNOWN 2025-09-11 Kettering, Ohio, 45249, United... More >> States|Oregon Health Science University, Portland, Oregon, 97239, United States|Springfield, Oregon, 97477, United States|Greenville, South Carolina, 29605, United States|Norfolk, Virginia, 23502, United States|Yakima, Washington, 98902, United States Less <<
NCT04668209 Coronavirus PHASE2 TERMINATED 2022-10-19 Banner University Medical Cent... More >>er Phoenix, Phoenix, Arizona, 85006, United States|Banner University Medical Center Tucson, Tucson, Arizona, 85724, United States Less <<
NCT05817708 COVID-19 PHASE1 COMPLETED 2023-06-20 Taipei Medical University Hosp... More >>ital, Taipei, 110301, Taiwan Less <<
NCT03897036 Carcinoma, Basal Cell PHASE1 ACTIVE_NOT_RECRUITING 2025-12-23 University of Colorado Anschut... More >>z Medical Campus, Aurora, Colorado, 80045, United States|H. Lee Moffitt Cancer Center & Research Institute, Inc., Tampa, Florida, 33612, United States|University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, United States|Inova Schar Cancer Institute, Fairfax, Virginia, 22031, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.86mL

0.57mL

0.29mL

14.30mL

2.86mL

1.43mL

28.59mL

5.72mL

2.86mL

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