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

Scoping Pleiotropy of CK2 in Musculoskeletal Disorders for a Novel Targeting Approach. (PubMed, Kinases Phosphatases) - "This review summarizes considerations for targeting CK2 in musculoskeletal disorders. We have discussed the implications of CK2-regulated processes in musculoskeletal disorders."

Journal • CNS Disorders • Musculoskeletal Diseases • Oncology • Osteoarthritis • Osteoporosis • Pain • Psychiatry • Rheumatology

Casein Kinase 1 and CK2 as Therapeutic Targets in Cancer: Molecular Pharmacology, Toxicological Considerations, and Clinical Progress. (PubMed, Mini Rev Med Chem) - "Several CK inhibitors, including CX-4945 (Silmitasertib), CIGB- 300, IC261, D4476, SR-3029, and BTX-A51, have shown promising anticancer activity in various cancer models. Novel dual-therapy approaches targeting CK1/CK2-regulated pathways have further improved the therapeutic specificity and efficacy. CK-targeting therapies are an exciting approach and hold great promise for selectively targeting cancer-causing signaling pathways and advancing cancer precision medicine."

Journal • Oncology

An Orally Available Derivative of a Specific CK2 Inhibitor for Regulating Circadian Rhythms and Acute Myeloid Leukemia. (PubMed, Precis Chem) - "The CK2 inhibitor CX-4945 is in clinical trials for cancer treatment, but it has many off-target proteins...After oral administration to mice, GO847 was detected in the plasma, liver, spleen, and bone marrow but not in the brain. Together, the findings show that GO847 is a promising candidate for targeting AML, a malignant blood cancer that requires effective treatment."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

GEM and Senhwa Biosciences have formally executed a Share Purchase Agreement for up to NT$500 million (PRNewswire) - "Purchases under the SPA may occur from time to time at the election of certain shareholders, subject to the terms and conditions of the SPA....Under the framework of the SPA, the equity commitment from GEM provides additional financial flexibility and is expected to support continued investment in Senhwa's clinical pipeline, potential in-licensing opportunities, and AI-enabled pipeline prioritization and expansion. The company's lead assets are CX-5461 (pidnarulex) and CX-4945 (silmitasertib), two investigational oncology therapies being studied across multiple cancer indications."

Commercial • Solid Tumor

HFPO-DA exacerbates acute ischemic stroke outcomes in rats via the CSNK2A1/GSK3B/NF-κB signaling pathway. (PubMed, Ecotoxicol Environ Saf) - "Moreover, in vivo CSNK2A1 inhibition with CX-4945 partially reversed the HFPO-DA-induced aggravation of ischemic injury. Collectively, our results suggest that HFPO-DA might be a potent environmental driver of post-ischemic neuroinflammation, likely acting in part via the CSNK2A1/GSK3B/NF-κB signaling pathway. These results provide novel insights into the specific neurotoxic mechanisms of HFPO-DA, highlighting its potential health risks in susceptible populations."

Journal • Preclinical • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Vascular Neurology

Blocking CK2α-Bclaf1 Preserves Oligodendrocytes After Neonatal Hypoxic Injury. (PubMed, Glia) - "Additionally, acute treatment with the clinically approved CK2 inhibitor silmitasertib and the herbal supplement curcumin not only reduces CK2α-Bclaf1 activity but also protects OLs and restores pre-myelinating ability in newborns following hypoxic injury. This approach unveils a key molecular regulation in hypoxia-related OL pathology and highlights a potential therapeutic strategy to mitigate neonatal hypoxic injury and prevent mental health complications."

Journal • Solid Tumor • Targeted Protein Degradation • BCLAF1

Phosphorylated DEK sustains leukemia stem cells by enabling PBX3-driven transcriptional reprogramming. (PubMed, Blood) - "Moreover, DEK deletion enhances LSC chemosensitivity to the standard-of-care combination of azacitidine and venetoclax (Aza/Ven), whereas DEK overexpression confers robust chemoresistance. Furthermore, combining CX-4945 with venetoclax promotes LSC apoptosis and represses the PBX3-driven leukemogenic transcriptional program, exhibiting synergistic anti-AML effects both in vitro and in vivo. Collectively, our findings uncover a previously unrecognized phosphorylation event (DEK-4S phosphorylation) that sustains LSCs and establish the CK2-DEK axis as a promising LSC-specific therapeutic strategy for AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • HOXA9 • MEIS1 • PBX3

A phase 1/2 and surgical Pediatric Brain Tumor Consortium (PBTC) study evaluating the casein kinase 2 (CK2) inhibitor CX-4945 (silmitasertib sodium) in children and adults with recurrent sonic hedgehog (SHH) medulloblastoma (MB): PBTC-053 (ISPNO 2026) - "CX-4945 was well tolerated in patients with recurrent SHH MB at doses reaching 800 mg/m2 twice daily, a final maximum tolerated dose was not determined. Early study closure restricts definitive conclusions; however the lack of an efficacy signal suggests limited activity in this patient population."

Clinical • P1/2 data • Biliary Tract Cancer • Brain Cancer • Medulloblastoma • Oncology • Pediatrics • Solid Tumor

EFFICACY OF BIOMIMETIC NANODRUG CX4945 IN B-ALL PATIENT-DERIVED XENOGRAFT MOUSE MODEL (EHA 2026) - "Summary/Conclusion Our results demonstrated the therapeutic efficacy of CX4945@PLGA-PEG@CM in high-risk B-ALL. Our data also revealed that CXCL12 on the biomimetic membrane of CX4945@PLGA-PEG@CM specifically targets the CXCR4-expressed B-ALL cells and enhances the drug efficacy, and also blocks the tumor cell homing."

Preclinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • CXCL12 • IKZF1 • PDX1 • PTPRC

THERAPEUTIC EFFECT OF CX-4945 COMBINED WITH XPO1 INHIBITOR BY TARGETING AMINO ACID METABOLISM IN T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2026) - "However, the effect of CX-4945 combined with XPO1 inhibitor KPT-330 in T-ALL has not been explored. (L) SLC7A5 expression in the mouse spleen upon the treatment for 28 days. *** P<0.001."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ANXA5 • CD7 • PTPRC • SLC7A5

PROTEIN KINASE CK2 AS A THERAPEUTIC HUB IN MANTLE CELL LYMPHOMA: FROM INFLAMMATION TO DRUG RESISTANCE (EHA 2026) - "Methods MCL cell lines were treated with CK2 inhibitors (CX-4945, SGC-CK2-1) or subjected to CK2 gene silencing alone and in combination with BETi (JQ-1, INCB054329). Summary/Conclusion These /ndings identify CK2 as a key driver of oncogenic transcription, infiammatory signaling, and adaptive resistance in MCL. CK2 inhibition disrupts tumor-promoting cytokine networks and restores sensitivity to BET inhibitors, supporting combination strategies aimed at enhancing therapeutic efficacy and overcoming drug resistance."

IO biomarker • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • BCL2 • BRD4 • CCL18 • CXCR4 • IFNG • IL10 • MYC • TGFB1 • TNFA

CK2 INHIBITION REPROGRAMS THE EPIGENETIC LANDSCAPE AND ENHANCES SENSITIVITY TO TARGETED THERAPY IN GERMINAL CENTER DIFFUSE LARGE B CELL LYMPHOMA (EHA 2026) - "Models were analyzed for viability, mechanistic signaling alterations, and histone modi0cation changes using puri0ed histone fractions after treatment with two distinct CK2 inhibitors, CX-4945 and the highly selective SGC-CK2-1. . Summary/Conclusion CK2 emerges as a central regulator of epigenetic balance in GCB-DLBCL, sustaining lymphoma survival through coordinated control of chromatin remodeling and BCL6 expression. Therapeutic targeting of CK2, especially in combination with tazemetostat, may provide a novel strategy to exploit epigenetic vulnerabilities in DLBCL."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • BCL2 • BCL6 • CREBBP • DNMT1 • EP300 • HDAC2 • LY9

ONCOGENIC ROLE AND DRUG SENSITIVITY OF A NEW IKZF1 MUTATION IN B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2026) - "(L) The expression of TCL1A in IKZF1S215P and vector only in Nalm6 cells by qPCR. (M) The expression of TCL1A in IKZF1S215P cells treated with CX-4945 alone, Chidamide alone, and two drugs combination for 48 h detected by RT-qPCR."

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

SYNERGISTIC THERAPEUTIC EFFICACY OF CDK9 INHIBITOR WITH CX-4945 BY REPRESSING ASNS TRANSCRIPTION IN HIGH-RISK B-ALL (EHA 2026) - "(M-N) The expression of ASNS in Nalm6 cells treated with CX-4945 alone, CDKI-73 alone, and two drugs combination for 48 h detected by RT-qPCR (M) and western blot (N). (O) Effect of ASNS knockdown versus shNC on cell proliferation in Nalm6 cells."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • ANXA5 • ASNS • PTPRC

THERAPEUTIC EFFECT OF TARGETING CASEIN KINASE II / PLK1 ONCOGENIC SIGNALING IN T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2026) - "(F-J) Spleen image (F), Spleen weights (G), % of human CD45 and CD7 positive T-ALL cells in the spleens (H) and bone morrow (I) and the survival (J) after T-ALL patient derived mouse model treated with Volasertib, CX-4945 and the combination for 28 days. *** P<0.001."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • CD7 • IKZF1 • PLK1 • PTPRC

SYNERGISTIC EFFECT OF COMBINED CK2 AND XPO1 INHIBITION IN PRECLINICAL MODELS OF ACUTE MYELOID LEUKEMIA: MECHANISM AND THERAPEUTIC POTENTIAL (EHA 2026) - "Single-agent inhibitors CX-4945 (CK2i) and selinexor (KPT-330, XPO1i) have shown limited efficacy. (S) Kaplan-Meier survival analysis showed that AML patients with low FOXO3 expression had significantly shorter overall survival in our center cohort and the GEO dataset GSE12417. (T) Anti-tumor mechanism model of the combination in AML."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • ANPEP • IKZF1 • PTPRC • XPO1

X-Linked USP11 Drives Depression-Like Behaviors by Stabilizing CK2α and Disrupting Mitochondrial Function. (PubMed, CNS Neurosci Ther) - "This study demonstrates that USP11 directly binds to and deubiquitinates CK2, affecting mitochondrial function in the mPFC and leading to depressive-like behaviors in mice."

Journal • CNS Disorders • Depression • Metabolic Disorders • Mood Disorders • Psychiatry • Targeted Protein Degradation • USP11

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs. (PubMed, Beilstein J Org Chem) - "Although ATP-competitive inhibitors such as CX-4945 show therapeutic potential, they are limited by off-target effects and incomplete or transient CK2 suppression...By conjugating a CAM4066-derived warhead to CRBN or VHL ligands, four VHL-recruiting PROTACs, were prepared using PEG and alkyl linkers, alongside two CRBN-recruiting analogues featuring constrained linkers. A ligand-linker analogue in which a linker is projected from the solvent-exposed region of CK2α retained binding affinity comparable to CAM4066, confirming that linker installation is tolerated and preserves key interactions in the αD and ATP sites."

Journal • Oncology • Targeted Protein Degradation • CRBN

Dynamic Phosphoproteomic Profiling Identifies Casein Kinase 2 as a Critical Survival Kinase in Quiescent Breast Cancer Cells and a Potential Therapeutic Target for Minimal Residual Disease. (PubMed, Cancers (Basel)) - "These findings establish CK2 as a critical survival kinase in QCCs and a potential therapeutic target for MRD eradication in breast cancer."

Journal • Minimal residual disease • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • DAPK3

Inhibition of protein kinase CK2 remodels the tumor immune microenvironment and sensitizes lung cancer to PD-L1 blockade. (PubMed, Exp Hematol Oncol) - "These findings identify CK2 as a key regulator of tumor immune evasion and uncover a previously unrecognized post-translational checkpoint controlling PD-L1 stability via TRAF6-dependent ubiquitination. Targeting CK2 represents a rational strategy to sensitize immunologically "cold" tumors to ICBs and enhance immunotherapeutic efficacy in lung cancer."

IO biomarker • Journal • Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CD8 • TRAF6

Therapeutic targeting protein kinase CK2 ameliorates lupus nephritis by modulating neutrophil infiltration and neutrophil extracellular trap formation. (PubMed, Arthritis Rheumatol) - "CK2α is aberrantly upregulated in SLE neutrophils, and targeting CK2 with CX-4945 exerts therapeutic effects in SLE. These findings identify CK2 as a novel therapeutic target for SLE and support the repurposing of CX-4945 for treating neutrophil-driven inflammatory and autoimmune diseases."

Journal • Dermatology • Glomerulonephritis • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Psoriasis • Septic Shock • Systemic Lupus Erythematosus

CX-4945 Shows Therapeutic Efficacy in Metastatic Ewing Sarcoma Xenograft and Organoid Models (ASPHO 2026) - P1/2 | "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."

Clinical • Metastases • Ewing Sarcoma • Sarcoma • Solid Tumor • CD99 • EWSR1 • FLI1 • GLI1

CK2 Inhibition as a Novel Strategy to Target MCL1 and Restore ABT-199 Sensitivity in Pediatric AML (ASPHO 2026) - "Background: Dysregulated signaling contribute to acquire resistance to regimens containing BCL2 (B-cell lymphoma-2) inhibitor, venetoclax (VEN; ABT-199), in acute myeloid leukemia (AML) and pose a clinical challenge. CX + VEN combo showed a superior antileukemic activity in different pre-clinical pediatric AML models including VR-AML cells. Our findings provide a mechanistic rationale for the use of clinical-grade CX-4945 (Silmitasertib) in combination with VEN as an effective approach for AML treatment and to circumvent VEN resistance."

Clinical • IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Leukemia • Lymphoma • Pediatrics • Solid Tumor • ANXA5 • GLI2 • MCL1 • TNFA • TP53

Novel Combination Therapy Targeting Polyamine Pathway in Neuroblastoma Pre-Clinical Models (ASPHO 2026) - P1/2 | "Results from preclinical studies support clinical testing. An ongoing Phase 1 study evaluates the safety of CX-4945 in relapsed refractory pediatric solid tumors, including NBL (NCT06541262)."

Combination therapy • Preclinical • Neuroblastoma • Solid Tumor • MYC • MYCN

Investigating synergistic effects with CK2 and C-KIT inhibition in B-ALL (AACR 2026) - "Given that imatinib is clinically used for Philadelphia chromosome-positive (Ph+) ALL, future work will assess CX-4945/imatinib synergy in Ph+ B-ALL, where an even more potent effect is anticipated. This combination approach may offer a promising therapeutic avenue for HR ALL subtypes characterized by IKZF1 alteration and chemotherapy resistance."

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