silmitasertib (CX-4945) / Senhwa Biosci, Cylene - LARVOL DELTA

Picomolar bivalent inhibitors of protein kinase CK2 active against β-coronavirus replication. (PubMed, Eur J Med Chem) - "In addition, Biv5 significantly reduced viral replication over time in an ex vivo model of primary human nasal epithelial cells. The selectivity of Biv5 was tested against 16 kinases targeted by CX-4945, confirming that targeting the αD pocket confers high selectivity for CK2 to such inhibitors."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

CK2 regulates somatostatin expression in pancreatic delta cells. (PubMed, Islets) - "The exposure of isolated murine and human islets to CX-4945 or SGC as well as the treatment of mice with CX-4945 revealed that CK2 also regulates SST expression under physiological conditions. Taken together, these findings not only demonstrate that CK2 controls SST expression in pancreatic δ-cells but also emphasize the crucial role of this kinase in regulating the main hormones of the endocrine pancreas."

Journal • KEAP1 • PDX1

CK2 in the spotlight: decoding its role in hematological malignancies and therapeutic applications. (PubMed, Discov Oncol) - "In recent years, a large number of studies have confirmed the therapeutic effect of targeting protein kinase CK2 in combination with other therapies in the treatment of hematological malignancies. Here, we reviewed the key signaling pathways regulated by protein kinase CK2, the role of protein kinase CK2 in various hematological malignant tumors, the research progress and the potential clinical application prospects."

Journal • Review • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor

Treatment Duration Increment and Pharmacodynamic Study of CX-4945 in Patients With Basal Cell Carcinoma (BCC) (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: Senhwa Biosciences, Inc. | Active, not recruiting ➔ Completed

Trial completion • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

THE SYNERGY OF HDACI CHIDAMIDE WITH CX-4945 ON THERAPEUTIC EFFICACY BY REPRESSING TCL1A TRANSCRIPTION IN HIGH-RISK B-ALL (EHA 2025) - "The combination of CHI with CX-4945 has a synergistic efficacy on cell proliferation inhibition, cell cycle arrest, and apoptosis in B-ALL cells by suppressing TCL1A in B-ALL cells. Our results also reveal the combinations suppress the leukemia engraftment in the B-ALL PDX mouse models. Our data provide experimental evidence for the combination as a potential option for high-risk B-ALL therapy."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • ANXA5 • IKZF1 • PTPRC • TCL1A

SYNERGISTIC EFFECTS OF NOVEL PROTEIN KINASE CK2 AND BET PROTEIN INHIBITORS IN MANTLE CELL LYMPHOMA: TARGETING SURVIVAL AND TUMOR-INDUCED IMMUNOSUPPRESSIVE SIGNALS (EHA 2025) - "We tested CX4945 and SGC-CK2-1, or CK2 gene silencing, with BET inhibitors (JQ-1, INCB054329) on MCL cells, assessing cell survival, apoptosis, and proliferation. The combined inhibition of CK2 and BET proteins represents a promising therapeutic approach targeting both intrinsic survival pathways that drive MCL progression and TME-related immunosuppressive signals that may contribute to therapy resistance. This dual-targeted strategy may open new avenues for improving immunotherapeutic responses in MCL, offering a rational approach to overcome current treatment limitations."

IO biomarker • Hematological Malignancies • Immunology • Lymphoma • Mantle Cell Lymphoma • Oncology • BRD4 • IGF1 • IL10 • MYC • PPBP • TIMP2

SYNERGISTIC INDUCTION OF APOPTOSIS BY DUAL CK2 AND BCL2 INHIBITION IN GERMINAL CENTER B-CELL-LIKE DIFFUSE LARGE B-CELL LYMPHOMA (EHA 2025) - "Patients with DHL involving BCL2 and THL, particularly those of the germinal center B-cell (GCB) subtype, exhibit aggressive disease behavior and poor responses to conventional R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy...The cytotoxic effects of SGC-CK2-1, CX-4945 and Venetoclax, both individually and in combination at a fixed ratio, were evaluated in the BCL2 rearranged OCI-LY1, OCI-LY19 and Pfeiffer GCB-DLBCL cell lines using cell viability assays... The results demonstrate that dual inhibition of CK2 and BCL2, induce enhances apoptosis in GCB-DLBCL cells, with a synergistic effect observed in the combination treatment. These findings highlight the therapeutic potential of concurrently targeting CK2 and BCL2 to overcome resistance mechanisms and improve treatment outcomes in aggressive, BCL2-rearranged GCB-DLBCL. Further studies are needed to evaluate the clinical applicability and translational relevance of this..."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ANXA5 • BCL2L1 • BCL6 • CASP3 • LY9 • MCL1 • MYC

THERAPEUTIC EFFICACY OF BIOMIMETIC NANODRUG CX4945 IN B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2025) - "CX4945@PLGA-PEG@CM has high therapeutic efficacy in the human B-ALL leukemia xenograft mouse model. Our results provide pre-clinical evidence for the new biomimetic nanodrug as a potential therapy option in ALL."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • CXCL12 • IKZF1 • PTPRC

THE SYNERGY OF DZNEP WITH CX-4945 AND THE CLINICAL RELEVANCE OF FOSL1 IN ACUTE MYELOID LEUKEMIA (EHA 2025) - "The combination of EZH2 inhibitor DZNeP and CK2 inhibitor CX4945 exerts a potent synergistic effect on proliferation arrest, cell cycle arrest, and apoptosis in AML by suppressing FOSL1 expression. Our results reveal the oncogenic role of FOSL1 in AML. Our data also provide experimental hints for the potential clinical trial of the novel combination in AML patients."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FOSL1

TARGETING THE CK2/IKAROS AXIS SENSITIZES IMATINIB ANTI-LEUKEMIA EFFICACY BY REPRESSING GLUT1 EXPRESSION AND GLYCOLYSIS IN PH+ ALL (EHA 2025) - "The combination of imatinib and CX-4945 has a synergistic anti-leukemia efficacy on leukemia development in Ph+ALL with IKZF1-deletion. Our data provide experimental evidence for a new potential combination of imatinib with CX-4945 in the therapy of Ph+ALL and highlight the likelihood of the novel combination in ALL patients."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • IKZF1 • PTPRC • SLC2A1

CX-4945 in Viral Community Acquired Pneumonia (clinicaltrials.gov) - P2 | N=45 | Terminated | Sponsor: Senhwa Biosciences, Inc. | N=136 ➔ 45 | Recruiting ➔ Terminated; The trial ended early in March 2025 due to changes in disease epidemiology, affecting patient availability and recruitment feasibility.

Enrollment change • Trial termination • Infectious Disease • Influenza • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

CK2 inhibitor shows anti-tumor activity in Ewing sarcoma preclinical models (AACR 2025) - P1/2 | "CX-4945 shows synergistic cytotoxic activity with Temozolomide and Irinotecan. CSNK2A1 expression is high in EWS and correlates with poor overall survival. CSNK2A1 expression is high in EWS and correlates with poor overall survival. CK2 inhibition decreases EWS-FLI protein abundance and suppresses its downstream target GLI1. CX-4945 shows excellent anti-tumor activity and target inhibition in EWS xenografts."

Preclinical • Ewing Sarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • EWSR1 • FLI1 • GLI1

Targeting the Her2 and ERα receptors has a significant impact on therapy-resistant ER-positive breast cancer (AACR 2025) - "We have shown that silmitasertib, a clinical phase CK2 inhibitor, can inhibit the proliferation of tamoxifen-sensitive and tamoxifen-resistant breast cancer cells in part by disrupting ERα/ERα variant expression. Our studies suggest that the development of ERαY537S mutations in BCa results in enhanced sensitivity to growth inhibition elicited by CK2 blockade. Our studies provide a convincing rationale for the therapeutic targeting of CK2 in the context of ERα-mutated, endocrine-resistant breast cancer."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CCND1 • ER • HER-2

CK2 inhibition exhibits synergistic effect with KIT inhibitors in acute lymphoblastic leukemia (AACR 2025) - "In conclusion, our results demonstrate that CK2 inhibitor, CX-4945, and c-KIT inhibitor, imatinib, exhibit a synergistic therapeutic effect on B-ALL cells. Presented data provide a rational for the use of combination therapy with CK2 inhibitors and imatinib for treatment of high-risk B-ALL, including Philadelphia positive (Ph+) B-ALL."

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • IKZF1

CK2 inhibition restores IKAROS-mediated metabolic control and induces cell death in acute lymphoblastic leukemia (AACR 2025) - "Treatment of ALL cell lines with the CK2 inhibitor CX4945 resulted in significant cell death, with IC50 values ranging from 4-10 µM...These findings demonstrate that CK2α inhibition effectively restores IKAROS-mediated metabolic control, leading to energy deficiency and increased oxidative stress in ALL cells. This work provides evidence that targeting the CK2-IKAROS axis represents a promising therapeutic strategy for ALL through metabolic modulation."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • IKZF1

Therapeutic efficacy of a novel combination of ck2 inhibitor cx-4945 with cytotoxic therapy in neuroblastoma preclinical models (AACR 2025) - P1/2 | "Protein kinase CK2 is intrinsically active and negatively impacts survival in HR-NBL patients. In MYCN-NBL xenograft models, CX-4945 is well tolerated and shows superior therapeutic efficacy when combined with cytotoxic drugs Irinotecan and temozolomide. The ongoing Phase 1/II study is evaluating the safety, tolerability, and efficacy of combining CX-4945 with TMZ+IRN in relapsed refractory NBL patients ((NCT06541262)."

Preclinical • CNS Tumor • Hematological Malignancies • Leukemia • Neuroblastoma • Oncology • Solid Tumor • MYCN

The dual targeting effects of KD025 on casein kinase 2 and ROCK2 in a mouse model of diet-induced obesity. (PubMed, Biochem Pharmacol) - "KD025(belumosudil), a selective ROCK2 inhibitor, exhibits unique anti-adipogenic activity through inhibition of casein kinase 2 (CK2)...C57BL/6 mice on a high fat diet (HFD) were treated with KD025 for 4 weeks, while fasudil (a pan-ROCK inhibitor) and CX-4945 (a CK2-specific inhibitor) served as comparison treatments...Furthermore, KD025 and CX-4945 upregulated adipogenic and browning markers, such as Cebpa, Cidea, and Pparg, in the epiWAT, though without significant UCP1 expression. Overall, KD025 effectively reduced weight gain in HFD-fed mice through dual inhibition of CK2 and ROCK2, highlighting its potential as a therapeutic agent for obesity-related conditions."

Journal • Preclinical • Genetic Disorders • Metabolic Disorders • Obesity • Oncology • CEBPA • IL6 • PPARG • TNFA

REPURPOSING AN ANTICANCER AGENT FOR THE TREATMENT OF HUNTINGTON'S DISEASE (ADPD 2025) - "These results establish CX4945 as a promising therapeutic agent for HD and reveal novel regulatory mechanisms of astrocytes in HD."

CNS Disorders • Huntington's Disease • Movement Disorders • Oncology

Senhwa Biosciences Announces Positive Clinical Data from Phase 1/Expansion Trial of Silmitasertib (CX-4945) in the Treatment of Basal Cell Carcinoma (PRNewswire) - P1 | N=25 | NCT03897036 | Sponsor: Senhwa Biosciences, Inc. | "Senhwa Biosciences...today announced that the completion of Clinical Study Report (CSR) for Phase 1/Dose Expansion Trial of Silmitasertib (CX-4945) in the Treatment of Basal Cell Carcinoma(BCC), with positive data outcomes....Among them, three patients experienced over 30% tumor reduction (PR), and two patients had a progression-free survival (PFS) exceeding 21 months. CX-4945 significantly prolonged survival in advanced cancer patients, marking a major milestone for both the patients and Senhwa....Further data analysis showed that: Median progression-free survival (PFS): laBCC: 9.2 months. mBCC: 3.7 months. Median duration of disease control (DDC): laBCC: 10.3 months. mBCC: 7.5 months." "

P1 data • Basal Cell Carcinoma

Assessment of repurposed compounds against coronaviruses highlights the antiviral broad-spectrum activity of host-targeting iminosugars and confirms the activity of potent directly acting antivirals. (PubMed, Antiviral Res) - "We observed 13 compounds showing antiviral activity against SARS-CoV-2, including seven FDA-approved compounds (remdesivir, boceprevir, amiloride, nafamostat, cisplatin, silmitasertib, and miglustat), and six compounds in pre-clinical and clinical development (tarloxotinib, lucerastat (NB-DGJ), MON-DNJ, NAP-DNJ, NN-DGJ and NN-DNJ). Its activity also extended to another betacoronavirus HCoV OC43, but not alphacoronavirus HCoV 229E. Our cellular screening results add to the body of knowledge on antivirals against coronaviruses and confirm the antiviral efficacy of iminosugars in cellular assays using the human lung-cell line Calu-3."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Single-cell and spatial transcriptomics reveal pre-metastatic subsets and therapeutic targets in penile carcinoma. (PubMed, iScience) - "Silmitasertib, a CK2α inhibitor, exhibited anti-tumor effects in penile carcinoma cells. Validated across 98 single-cell and 6 spatial datasets, our study advances the understanding of tumorigenesis and metastasis, highlighting Silmitasertib as a potential therapeutic agent."

Journal • Genito-urinary Cancer • Infectious Disease • Oncology • Penile Cancer • Solid Tumor • Squamous Cell Carcinoma • MMP3 • SPP1

Spatio-temporal Progression of Focal Ischemic White Matter Injury (ISC 2025) - "We established MRI modalities to longitudinally assess WMI damage which correlates with behavioral deficits and cellular and molecular damage. Additionally, we showed that CX-4945 exerts post-ischemic protection of WM integrity quantified with MRI images, decreased NOX activity, and improved mitochondrial function."

Late-breaking abstract • Cardiovascular • Ischemic stroke • Metabolic Disorders

CK2 inhibition as a promising treatment for chemotherapy resistant pancreatic ductal adenocarcinoma (LCC 2025) - "Using the first-in-class, CK2-selective inhibitor CX-4945/Silmitasertib, shown to be safe and well-tolerated in phase I/II clinical trials for cholangiocarcinoma, medulloblastoma, and basal cell carcinoma7, and well defined in vitro and in vivo models of PDAC validated in our laboratory, we aim to investigate the impact of CK2 inhibition on PDAC tumorigenesis, metastasis, chemoresistance, and immune infiltration...Notably, nuclear accumulation of CK2 is a reliable predictor of poor prognosis8. We hypothesise that inhibition of CK2 will reduce metastasis and improve overall survival in in vitro and in vivo models of PDAC by sensitising PDAC cells to the latest clinically used chemotherapies by inhibiting CK2-driven DNA damage repair pathways, and promoting activation of the existing immune system."

IO biomarker • Basal Cell Carcinoma • Biliary Cancer • Brain Cancer • Cholangiocarcinoma • Medulloblastoma • Non-melanoma Skin Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Phosphoproteomic analysis identifies casein kinase II and MAPK signaling inhibition as a therapeutic strategy for metastatic colorectal cancer (LCC 2025) - "In particular, the combination between silmitasertib and trametinib, a selective inhibitor of MEK1/2, induced a simultaneous reduction of mTORC1, MAPK and CKII signaling compared to either drug alone. Additionally, the dual therapy significantly reduced active β-catenin levels and decreased the pool of CD44/CD133 double-positive cancer stem cells, which are critical in therapy resistance. Taken together, our findings highlight the potential of phosphoproteomic analysis to strategically inform and advance cancer therapy and propose a promising new therapeutic opportunity for mCRC patients, warranting further preclinical and clinical investigations."

Metastases • Omic analysis • Colorectal Cancer • Oncology • Solid Tumor • CD133 • KRAS

Targeting the IKZF1/BCL-2 axis as a novel therapeutic strategy for treating acute T-cell lymphoblastic leukemia. (PubMed, Cancer Biol Ther) - "In vivo studies with cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models demonstrated that CX-4945 and venetoclax combined therapy provided superior therapeutic efficacy, reducing tumor burden and prolonging survival compared to single-agent treatments. IKZF1 represses BCL-2 in T-ALL, and targeting the CK2-IKZF1 axis with CX-4945 and venetoclax offers a promising therapeutic strategy, showing enhanced efficacy and potential as a novel treatment approach for T-ALL."

IO biomarker • Journal • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • BCL2 • IKZF1