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

Clinical trial in progress: BCC021 Phase I/II study of Silmitasertib (CX-4945) in combination with chemotherapy in children and young adults with relapsed refractory solid tumors (AACR 2026) - "Abstract is embargoed at this time."

Clinical • Combination therapy • P1/2 data • Oncology • Solid Tumor

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

Quantitative phospho-proteomics uncovers CX-4945 effects on translational control and differentiation in neuroblastoma (AACR 2026) - "Protein kinase CK2 is intrinsically active and negatively impacts survival in HR-NBL patients. Phospho-proteomic analysis reveals, changes in multiple pathways which leads to reduced proliferation and increased neuronal differentiation."

Ewing Sarcoma • Hematological Malignancies • Leukemia • Neuroblastoma • Oncology • Sarcoma • Solid Tumor • EIF4A1 • IRS4 • MYCN

Clinical-grade CK2 inhibitor CX-4945 synergistically enhances venetoclax-mediated antileukemic activity in preclinical acute myeloid leukemia models (AACR 2026) - "CX+VEN combo showed a superior antileukemic activity in different pre-clinical AML models and CK2 inhibition overcome VEN resistance. CX-4945 (Silmitasertib) has favorable pharmacokinetics with good tolerability in human studies and is being evaluated in early phases of clinical trial. Our findings provide a rationale for CK2 and BCL2 co-targeting as an effective approach for AML treatment and to overcome VEN resistance."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • B Cell Lymphoma • Leukemia • Lymphoma • Oncology • Solid Tumor • ANXA5 • BCL2 • CD123 • CD34 • CD38 • GLI2 • IL3RA

Therapeutic efficacy of CK2 inhibitor in patient-derived lung metastatic model of Ewing sarcoma (AACR 2026) - P1/2 | "These results support further preclinical characterization and mechanistic investigation of CX-4945 for treating ES. A phase 1 clinical trial is evaluating the safety of CX-4945 in pediatric solid tumors, including ES (NCT06541262). Patient derived lung metastasis model of Ewing sarcoma development and assessment for effect of treatment is feasible and essential to determine clinically meaningful therapeutic effect of anti-cancer agent."

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

Combining Temozolomide with a Selective CK2 Inhibitor Results in Anti-Tumour Effects in Glioblastoma Cell Lines. (PubMed, Molecules) - "In this study, we found that TF effectively reduces the proliferation of A1207 glioblastoma cells with an EC50 value of 13.7 µM, which is equal to the EC50 value of CX-4945, which was the first CK2 inhibitor in clinical phase II trials (13.9 µM). The decrease in proliferation and viability is partly due to the induction of apoptosis, with both cell lines differing in terms of the pattern of apoptotic caspases. Taken together, TF in combination with TMZ may be a promising candidate for the treatment of glioblastoma in the future."

Journal • Preclinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Enhancing tyrosine kinase inhibitor sensitivity by restoring IKAROS activity on GLUT1 expression and glycolysis in Philadelphia chromosome-positive acute lymphoblastic leukemia. (PubMed, Leukemia) - "The combination of TKIs (imatinib or ponatinib) with CX-4945 significantly extended the survival and reduced the tumor burden in the IKZF1 deletion (Ik6+) Ph+ ALL patient-derived xenograft (PDX) mouse model; particularly, the patient died of relapse shortly after treatment with the third-generation TKI and the CD19/CD3 bispecific antibody blinatumomab. The combination of TKIs with CX-4945 demonstrates the synergistic efficacy through restoring IKAROS transcriptional repression of GLUT1 and further suppressing glycolysis in Ph+ ALL. Our results identify new mechanisms underlying TKI sensitivity and novel approaches to overcome TKI resistance through transcriptional repression of the key genes in glycolysis in Ph+ ALL."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • IKZF1 • SLC2A1

Transcriptional regulation of CD19 by IKZF1 enhances CAR T-Cell immune targeting in mantle cell lymphoma (AACR-IO 2026) - "Parallel experiments leveraged CK2α inhibition with silmitasertib to increase endogenous IKZF1 protein stability via reduced proteasomal turnover...In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr C009."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • CD19 • IFNG • IKZF1

Senhwa Biosciences Signs Major Strategic MOU with Y Combinator-Backed AI Biotech Company CellType to Accelerate the Evolution of CX-4945 into Version 2.0 and Reshape the Global Immunotherapy Landscape (PRNewswire) - "Under this partnership, the two companies will integrate CellType's proprietary AI platform to accelerate the clinical development and global commercialization strategy of Senhwa's core asset, Silmitasertib (CX-4945)....Under the MOU, the parties will initiate a six-month pilot program focused on: Indication expansion strategies, Biomarker discovery and validation, Combination therapy synergy evaluation in the context of immuno-oncology and new targets for treating different types of cancers and Establishment of an AI-driven translational validation framework."

Licensing / partnership • Oncology

Inhibiting CK2 in breast cancer: From molecular targets to drug candidates. (PubMed, Eur J Med Chem) - "Over the past decades, a wide range of CK2 inhibitors has been developed ranging from classical ATP-competitive scaffolds (TBB, DMAT, CX-4945) to highly selective second-generation chemical probes (SGC-CK2-1, AB668) and substrate-targeting peptides (CIGB-300). Preclinical evidence highlights strong antitumor effects of CK2 blockade in hormone-refractory and triple-negative breast cancer (TNBC), with additional potential to overcome endocrine and chemoresistance. This review integrates recent advances in CK2 biology, summarizes the evolution of CK2 inhibitor classes, and outlines the opportunities and remaining barriers for translating CK2 inhibition into effective cancer therapeutics."

Journal • Review • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CTNNB1 • STAT3

Silmitasertib, an FDA-designated orphan CK2 inhibitor, ameliorates neuropathology and motor dysfunction in a Huntington's disease mouse model. (PubMed, Neurotherapeutics) - "Importantly, we found CX-4945 decreased mHtt aggregation, increased DARPP-32 protein levels and excitatory synapse density, restored homeostatic astrocyte phenotypes and ameliorated neuroinflammation and microgliosis, altogether resulting in improved motor behavior. These results support CX-4945 as a strong candidate for a targeted therapy to treat HD."

Journal • Preclinical • CNS Disorders • Huntington's Disease • Inflammation • Movement Disorders

Switching off CK2-mediated activation of survivin offers new therapeutic opportunities in neuroblastoma. (PubMed, Exp Mol Med) - "In particular, here we report on the identification of CK2-TN03, a CK2 inhibitor showing greater selectivity and cellular efficacy than silmitasertib, the only available clinical grade CK2 inhibitor with orphan status for cholangiocarcinoma and in clinical trials for medulloblastoma...Accordingly, neuroblastoma cells persistently stall in mitosis before going to apoptosis. Finally, CK2-TN03 does not affect noncycling cells and significantly reduces tumor growth in mice xenografts without any apparent toxicity."

Journal • Biliary Cancer • Brain Cancer • Cholangiocarcinoma • Medulloblastoma • Neuroblastoma • Oncology • Solid Tumor • AKT1 • BIRC5 • BRD4 • MYCN

CK2 inhibitor, CX-4945, enhances BH3 priming and promotes apoptosis of venetoclax-resistant AML by targeting antiapoptotic proteins. (PubMed, bioRxiv) - "CX-4945 (silmitasertib) is being tested in several early-phase clinical trials against adult and pediatric cancers. These preclinical results support the use of CX-4945 in combination with VEN to overcome resistance to apoptosis and re-sensitize VR-AML to chemotherapy."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • BCL2A1 • BCL2L1 • CD123 • CD34 • CD38 • IL3RA • MCL1

Targeting the casein kinase II /ikaros axis sensitizes TKI activity by suppression of GLUT1 expression and glycolysis in ph+ ALL (ASH 2025) - "Results showed that the combination of various doses of TKI Imatinib orPonatinib with 2.5 μM (1/2 IC50) or 5 μM (IC50) CX-4945 showed significant synergistic effects on the cellproliferation arrest of Sup-B15 cells (CalcuSyn analysis CI < 1, and the Bliss model synergy score of 6.617or 5.885, respectively). CX-4945 sensitizes the sensitivity of TKI activity in Ph+ALL, particularly with IKZF1 deletion,by affecting GLUT1 expression and glycolysis. Our findings reveal the potential of the new combination inthe therapy of ALL patients."

Acute Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • ANXA5 • IKZF1 • PTPRC • SLC2A1

Combined Inhibition of Protein Kinase CSNK2 and BET Proteins As a Novel Therapeutic Strategy for Mantle Cell Lymphoma (ASH 2023) - "Currently available therapeutic approaches for Mantle Cell Lymphoma (MCL), including the Bruton Tyrosine Kinase (BTK) inhibitors ibrutinib, acalabrutinib and zanubrutinib, are not curative...In MCL, BET inhibitors, such as INCB054329 or JQ-1, have been shown to increase apoptosis through downregulation of the AKT-mTOR, ERK, and other B Cell Receptor (BCR)-triggered cascades...The most effective and tested CSNK2 chemical inhibitor is CX4945 (silmitasertib), but very recently a novel compound, SGC-CK2, has been developed...Remarkably, CK2 inactivation led to a robust reduction of the BET inhibitor-induced increase of Mcl1, and NF-kB Ser 529 phosphorylation, thus counteracting BET-inhibitors-evoked compensatory pathways that could favor apoptosis resistance. Therefore, combined CSNK2 and BET proteins inhibition could represent an innovative strategy for chemotherapy and BTKi-resistant MCL."

Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • ANXA5 • BRD4 • MYC

Silmitasertib, an FDA-designated orphan CK2 Inhibitor, ameliorates neuropathology and motor dysfunction in a Huntington's disease mouse model. (PubMed, bioRxiv) - "Importantly, we found CX-4945 decreased mHtt aggregation, increased DARPP-32 expression and excitatory synapse density, restored homeostatic astrocyte phenotypes and ameliorated neuroinflammation and microgliosis, altogether resulting in improved motor behavior. These results support CX-4945 as a strong candidate for a targeted therapy to treat HD."

Journal • Preclinical • CNS Disorders • Huntington's Disease • Inflammation • Movement Disorders

Macropinocytosis as a novel target for pediatric high grade glioma therapy (SNO 2025) - "In addition, silmitasertib synergizes with temozolomide to decrease cell proliferation (ZIP synergy score = 15.23). These findings suggest that pHGGs undergo macropinocytosis in vitro and targeting this pathway may be an additional avenue for therapy. In addition, to further understand the genetic signatures underlying macropinocytosis, we are currently conducting a targeted CRISPR screen with an endocytosis, macropinocytosis, phagocytosis, and lysosomal processing library."

Clinical • Brain Cancer • Glioma • High Grade Glioma • Pediatrics • Solid Tumor

Synergistic Effect of CK2 Inhibitor CX-4945 with HDACi Chidamide on Cell Proliferation Arrest and Apoptosis in Acute Myeloid Leukemia (ASH 2023) - "Our data provide experimental evidence for the combination as a potential option for AML therapy. More pre-clinical studies will be explored for future clinical trials."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • IKZF1 • MYC • PIK3CD

Scaling Large Language Models for Next-Generation Single-Cell Analysis. (PubMed, bioRxiv) - "This predictive strength directly enabled a dual-context virtual screen that uncovered a striking context split for the kinase inhibitor silmitasertib (CX-4945), suggesting its potential as a synergistic, interferon-conditional amplifier of antigen presentation. Experimental validation in human cell models unseen during training confirmed this hypothesis, demonstrating that C2S-Scale can generate biologically grounded, testable discoveries of context-conditioned biology. C2S-Scale unifies transcriptomic and textual data at unprecedented scales, surpassing both specialized single-cell models and general-purpose LLMs to provide a platform for next-generation single-cell analysis and the development of "virtual cells.""

Journal

Macropinocytosis as a novel target for pediatric high grade glioma therapy (WFNOS 2025) - "In addition, silmitasertib synergizes with temozolomide to decrease cell proliferation (ZIP synergy score = 15.23). These findings suggest that pHGGs undergo macropinocytosis in vitro and targeting this pathway may be an additional avenue for therapy. In addition, to further understand the genetic signatures underlying macropinocytosis, we are currently conducting a targeted CRISPR screen with an endocytosis, macropinocytosis, phagocytosis, and lysosomal processing library."

Clinical • Brain Cancer • Glioma • High Grade Glioma • Pediatrics • Solid Tumor

Casein Kinase II Inhibitor Sensitizes the Anti-Tumor Effect of EZH2 Inhibitor By Suppressing FOSL1 Expression in Acute Myeloid Leukemia (ASH 2023) - "The present study aims to investigate the effect of the combination of the EZH2 inhibitor DZNeP with CK2 inhibitor CX4945 in AML and possible underlying mechanisms...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."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • EZH2 • FOSL1

Suppressing IKZF1 Deletion-Mediated Activation of Ras Oncogenic Signaling By the Combination of Azacitidine and Flumatinib in High-Risk B-ALL (ASH 2023) - "Moreover, about 80% of Ph +B-ALL patients have the IKZF1 deletion, our ChIP-seq data showed that IKZF1-encoded Ikaros protein binds to the promoter region of PTPN11 and CK2 inhibitor CX4945 as Ikaros function activator dramatically increase the Ikaros binding to the promoter of PTPN11 in B-ALL cells and Ikaros directly suppresses its promoter activity (Fig. Conclusions The combination of AZA and FLU has a synergistic anti-leukemia effect on cell proliferation arrest and apoptosis in Ph +ALL cells with IKZF1-deletion by targeting Ikaros/PTPN11/Ras oncogenic signaling. Our data provide experimental evidence for a new potential combination of AZA with FLU in the therapy of Ph +ALL and highlight the likelihood of the novel combination in ALL patients."

IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • BCL2 • CDKN1A • IKZF1 • PTPN11

Dual Targeting Novel WDR5/ATAD2 Oncogenic Signaling through CK2/Ikaros Axis Demonstrates Synergistic Efficacy in T-ALL (ASH 2023) - "RNA-seq was performed after CEM cells were treated with WDR5 inhibitor (OICR-9429), CX-4945 and vehicle control for 72 hours. Our study reveals a model that dual targeting WDR5/ATAD2 signaling through direct inhibiting oncoproteins and via CK2/IKAROS axis to transcriptionally repress the oncoprotein to achieve synergistic efficacy. Our results further highlight the combination of CX-4945 with WDR5 inhibition is a potential option for the therapy of T-ALL patients."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ATAD2 • IKZF1 • PTPRC • WDR5

Selinexor Synergizes CX4945 on Anti-Tumor Effect By Targeting XPO1/Ikros/c-Myc Signaling in T-Cell Acute Lymphoblastic Leukemia (ASH 2023) - "Conclusions The combination of Selinexor and CX4945 has synergistic effects on cell proliferation arrest and apoptosis in T-ALL by targeting the XPO1/IKROS/c-Myc signaling. Our results also provide experimental evidence for the new combination of Selinexor and CX4945 as a new potential therapeutic option for T-ALL patients."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ANXA5 • IKZF1 • XPO1

Synergistic Effect of CK2 Inhibitor CX-4945 with HDACi Chidamide in B-Cell Acute Lymphoblastic Leukemia By Downregulating TCL1A Expression (ASH 2024) - "Moreover, TCL1A knockdown significantly suppresses the proliferation of B-ALL cell lines (p<0.05).Conclusion Our results indicate that the combination of CX-4945 and CHI exerts an anti-leukemic effect by suppressing TCL1A expression in B-ALL. Our study reveals a new potential combination therapy for high-risk B-ALL."

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