Structure of Silmitasertib
CAS No.: 1009820-21-6
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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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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Purchased from AmBeed: 61825-94-3 ; 1009820-21-6 ; 444731-52-6 ; 85622-93-1 ; 557795-19-4 ; 755037-03-7 ; 849217-68-1 ; 15663-27-1 ; 284461-73-0 ; 417716-92-8 ; 51-21-8
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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 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Target |
|
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 << |
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 |
Tags: Silmitasertib | CX-4945 | CX4945 | CX 4945 | Casein Kinase | Autophagy | CK2 inhibitor | casein kinase 2 | serine/threonine kinase | cell cycle progression | DNA damage response | glioblastoma | leukemia | 1009820-21-6
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