sepantronium bromide (PC-002)
/ Astellas, Cothera Biosci
- LARVOL DELTA
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December 03, 2025
Strategic trimodal therapy enhances radiation-induced abscopal response in renal cancer.
(PubMed, J Transl Med)
- "This study presents a novel and effective strategy to induce the abscopal effect through a synergistic combination of targeted drug delivery, radiotherapy, and immunotherapy. The approach offers strong translational potential for improving radioimmunotherapy outcomes in renal and potentially other immunogenic cancers."
Journal • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD163 • CD8 • IL2
October 31, 2025
Whole-genome doubling promotes immune evasion in TNBC by epigenetically silencing antigen presentation pathways through PRC2 activity.
(SABCS 2025)
- "Through single-cell profiling, we found that WGD+ cancer cells exhibit impaired antigen presentation, driven in part by a reduced response to IFN-γ and epigenetic silencing of MHC class I transcriptional regulators via the PRC2 complex.Treatment with a PRC2 inhibitor preferentially inhibited WGD+ tumor growth, restored antigen presentation, and enhanced CD8⁺ T cell infiltration. These findings suggest that combined inhibition of PRC2 and PD-1 represents a promising therapeutic approach for WGD+ breast cancers."
Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Triple Negative Breast Cancer • CD8 • HER-2 • IFNG
December 11, 2025
From bioinformatics to clinical translation: BIRC5 as a pivotal diagnostic biomarker and therapeutic target for NAFLD-driven HCC.
(PubMed, Cell Biol Toxicol)
- "This study proposes BIRC5 as a therapeutic target and diagnostic biomarker, offering perspectives for HCC diagnosis and treatment of HCC. These results underscore the importance of BIRC5 in halting NAFLD-HCC progression and provide valuable insights for future clinical applications."
Biomarker • Journal • Addiction (Opioid and Alcohol) • Fibrosis • Gastroenterology • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor • BIRC5 • CCNB1 • CDK1 • TOP2A
November 20, 2025
Mapping the Progression of Therapy-Induced Senescence to Therapy Tolerance: An Evolutionarily Conserved Mechanism for Optimizing Cancer Treatment with Senotherapeutics.
(PubMed, ACS Pharmacol Transl Sci)
- "However, this was most effective within a specific time window after TIS induction. We suggest that the timely use of senotherapeutics could improve the effectiveness of anticancer drugs in clinical settings."
Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • TGFB1
November 27, 2025
YM155 Inhibition of Survivin Enhances Carboplatin Efficacy in Metastatic Castration-Resistant Prostate Cancer.
(PubMed, Pharmaceuticals (Basel))
- "YM155 (Sepantronium bromide) suppresses survivin expression and has demonstrated antitumor activity in preclinical models. The integration of clinical and functional data provides translational support for combining the survivin inhibitor YM155 with platinum-based therapy. These results warrant further validation in larger patient cohorts and in vivo models."
Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor
November 28, 2025
Multiplexed Transcriptomics for Screening Drug Combinations and Defining the Mechanism of Action of HCC Therapeutics at Single-Cell Resolution.
(PubMed, Cell Prolif)
- "A gene regulatory network analysis highlighted JUN as a key regulator mediating proliferation inhibition, primarily active in the apoptotic cell subcluster. These findings illustrate how integrating high-throughput screening with mechanistic dissection can accelerate the discovery of targeted drug combination therapies, and offer a blueprint for precise interventions using pathway vulnerabilities and cellular heterogeneity in HCC."
Journal • Hepatocellular Cancer • Oncology • Solid Tumor
November 14, 2025
Integrating bulk and single-cell RNA sequencing analysis to reveal characterization of mechanical stimulus-related genes and prognostic signatures in breast cancer.
(PubMed, Breast Cancer Res)
- "We developed a pioneering prognostic signature incorporating MSRGs in breast cancer, with a particular focus on mechanical stimuli may influence breast cancer prognosis by remodeling the immune microenvironment. The findings highlighted the importance of personalized treatment strategies and provide new insights into the role of mechanical forces in breast tumor biology."
Journal • Breast Cancer • Oncology • Solid Tumor
December 03, 2023
Single-Cell Multi-Ome Analysis Reveals Novel Molecular Mechanisms Underlying Subclonal Response to Survivin Inhibition in Relapsed/Refractory Multiple Myeloma
(ASH 2023)
- "An earlier study has shown that YM155 enhances daratumumab-mediated cellular lysis of multiple myeloma cells. Our RNAseq and CyTOF results thus suggest a potential basis of synergy between YM155 with immunotherapies approved for myeloma, which we will test further. Our approach thus integrates in silico prediction with single-cell multi-ome analysis to identify molecular mechanisms potentially underlying subclonal response to novel combination therapy candidates (secDrugs) for the treatment of RRMM."
IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • ATF3 • BIRC5 • CD81 • CDC37 • DDIT3 • PD-L1
November 03, 2023
Treatment of Relapsed/Refractory Hgbcl and Bukitt's Lymphoma with c-Myc Rearrangement: A Multi-Center, Open-Label, Phase 2 Study of PC-002 (SepB), a First-in-Class Deubiquitinase Inhibitor Inducing Myc Degradation
(ASH 2023)
- P2 | "PC-002 (also known as Sepantronium Bromide, or SepB) is a small molecule previously identified as a survivin suppressant with antitumor activity against a range of tumor types... At the time of abstract submission, the 1st cohort (3.6 mg/m2/day) of 3 patients have completed at least four cycles of treatment. PC-002 is generally well-tolerated at 3.6 mg/m2/day and progression to Cohort 2 at a dose of 4.8 mg/m2/ day was approved by the Safety Review Committee. Two patients with relapsed/refractory Burkitt Lymphoma at the starting dose of 3.6 mg/m2/day achieved a confirmed PR."
Clinical • P2 data • Anemia • B Cell Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • BIRC5 • MYC
December 07, 2024
YM155 Exerts Anti-Myeloma Effects Via Myc/BBC3 Signaling Pathway in Vitro
(ASH 2024)
- "The combination of YM155 and bortezomib showed superior cytotoxicity compared to either agent alone, suggesting a synergistic effect...YM155 exerts its anti-myeloma effects by inhibiting Myc and upregulating BBC3 expression, which activates the P53 pathway. This provides its potential role for the treatment of high-risk/relapsed refractory MM."
IO biomarker • Preclinical • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • BBC3 • BCL2 • MYC
December 07, 2024
PC-002 (Sepantronium Bromide) Enhances the Antitumor Efficacy of Anti-CD20 Antibody By CD20 Upregulation
(ASH 2024)
- "P493 tet-off cells were treated with tetracycline to suppress the expression of c-Myc (Myc-off)...Furthermore, mouse xenografts (RAMOS, SU-DHL-4, SU-DHL-10 and OCI-LY7) were established to evaluate the efficacy of YM155 (2 mg/kg, 168-hour-infusion) in combination with anti-CD20 antibody, including Rituximab, Ripertamab and Ofatumumab in vivo...Moreover, the up-regulation of CD20 after PC-002 treatment in RFP/Luc cells was confirmed by whole transcriptome analysis. These results indicate that PC-002 enhances the efficacy of anti-CD20 antibody by downregulating c-Myc, and support the planned clinical investigation of the combination of PC002 with an anti-CD20 antibody such as rituximab in patients with relapsed/refractory c-Myc driven Burkitt lymphoma or diffuse large B-cell lymphoma.Conclusion : In conclusion, our preclinical data highlight the potent anti-tumor effects of PC-002 in combination with anti-CD20 antibody in patients with DLBCL and BL, and warrant the planned..."
Clinical • B Cell Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Orthopedics • Solid Tumor • Targeted Protein Degradation • MYC • USP7
November 06, 2024
Study of PC-002 (Sepantronium Bromide), a First-in-Class Inhibitor of Deubiquitinases (DUBs) Targeting Myc Degradation in Relapsed/Refractory c-Myc Rearranged High-Grade B Cell Lymphoma (HGBCL): Updated Phase 2 Results
(ASH 2024)
- P2 | "Background : C-Myc rearrangement is a hallmark of high-grade B-cell lymphoma (HGBCL) and Burkitt lymphoma (BL) [1], effective treatment for relapsed/refractory disease represents an unmet need. Conclusions : PC-002 monotherapy demonstrated high clinical activity in heavily pretreated BL patients with a good safety profile. Initial successful salvage attempt with the addition of Rit suggests that a SepB-Rit combination will lead to greater clinical benefit, and warrants further clinical investigation of the combination of PC002 with rituximab in patients with relapsed/refractory c-Myc driven Burkitt lymphoma or diffuse large B-cell lymphoma."
P2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • BIRC5 • MYC
October 29, 2025
Advancing prognostic and therapeutic prediction in lung squamous cell carcinoma through integrated multi-omics analysis and 117 machine learning combinations.
(PubMed, J Thorac Dis)
- "The optimal prognosis signature (OPS) was constructed based on the CC-related genes and 117 ML algorithms in early- and advanced-stage LUSC, with data sourced from TCGA, GSE157011, GSE73403, GSE37745, and GSE14814 cohorts...AZD6482_2169 and Selumetinib_1736 were identified as potential therapeutic agents for the high OPS group...Additionally, sepantronium bromide_1941 was identified as a potential therapeutic agent for the high OPS group. The single-cell analysis suggested that the OPS-related genes were predominantly expressed in epithelial cells. This study developed a novel approach for the precise and individualized treatment of LUSC patients using advanced ML and multi-omics integration technology."
Journal • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma
October 29, 2025
YM155 Restores the Effect of Imatinib in Imatinib-Resistant Chronic Myeloid Leukemia Cell Lines.
(PubMed, Curr Cancer Drug Targets)
- "YM155 enhances imatinib's efficacy against both sensitive and resistant CML cells, overcoming resistance through synergistic inhibition of proliferation, increased apoptosis, and suppression of survivin and BCR::ABL1 expression. These results support further investigation of YM155-Imatinib combination therapy as a potential strategy for resistant CML."
Journal • Preclinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Oncology • ABL1
October 16, 2025
Interplay of PRMTs and Identification of Biomarkers Through Machine Learning Algorithms in Pan-Cancer, Highlighting PRMT3 as a Biomarker in Pancreatic Cancer.
(PubMed, FASEB J)
- "Daporinad, dinaciclib, and sepantronium bromide were predicted as potential drugs for the majority of cancer types. Potential biomarkers had been identified that may predict responses to immunotherapy and improve survival outcomes for cancer patients. This study provided a detailed overview of the functional roles, genetic and epigenetic alterations, and prognostic significance of PRMTs in pan-cancer."
Biomarker • IO biomarker • Journal • Pan tumor • Oncology • Pancreatic Cancer • Solid Tumor • PRMT3
October 12, 2025
Patient-Derived Tumoroid Xenograft Models for Preclinical Validation of Therapeutics in Pleural Mesothelioma
(IMIG 2025)
- "We tested the efficacy of romidepsin (a histone deacetylase inhibitor), sepantronium bromide (SB; a survivin inhibitor), and cisplatin-pemetrexed (CP; standard of care). These tumoroid-based xenograft models effectively recapitulate PM heterogeneity and provide a robust platform for therapeutic testing. Preliminary findings suggest survivin inhibition with sepantronium bromide as a promising strategy, meriting further experiments on different tumoroid cultures. In addition, further drug candidates showing promising yet more tumor-specific susceptibility profiles are currently under investigation, including ixazomib, a proteasome inhibitor, and ganetespib, a heat shock protein 90 (HSP90) inhibitor."
Preclinical • Giant Cell Tumor of Bone • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • BIRC5 • CDC37 • HSP90AA1 • VIM
September 27, 2025
Evaluation of a Novel Pan-RAS Inhibitor in 3D Bioprinted Tumor Models.
(PubMed, Cancers (Basel))
- " Potency and selectivity of ADT-007 were benchmarked against bortezomib (proteasome inhibitor) and YM155 (survivin inhibitor) using high-content imaging and ATP-based luminescence assays...This study also underscores the translational utility of 3D BEST models for preclinical drug response assessment. Further validation in patient-derived BEST is necessary to evaluate the potential of ADT-007 in clinical settings."
Journal • Preclinical • Colorectal Cancer • Oncology • Solid Tumor • ANXA5 • KRAS
September 16, 2025
Survivin as a Multifaceted Oncogenic Driver and Therapeutic Target in Renal Cell Carcinoma.
(PubMed, bioRxiv)
- "Collectively, these findings identify survivin as a multifaceted oncogenic driver in RCC that integrates cell cycle progression, cytoskeletal organization, and mitochondrial homeostasis. By revealing survivin's dual roles in proliferative and metabolic adaptation, this work highlights survivin as both a prognostic biomarker and a therapeutic vulnerability, supporting future strategies that combine survivin inhibition with metabolic or cell cycle-directed therapies for advanced kidney cancer."
Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • BIRC5 • CCND1
July 30, 2025
Comprehensive analysis of cholesterol metabolism-related genes in prostate cancer: integrated analysis of single-cell and bulk RNA sequencing.
(PubMed, Discov Oncol)
- "The CMG-based prognostic model effectively predicts prognosis in PRAD patients and is linked to distinct biological pathways, immune landscapes, and drug sensitivities. This signature has the robust potential to guide personalized therapy and improve prognosis in PRAD."
Journal • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor
July 29, 2025
The chemical instability of the survivin inhibitor - sepantronium bromide (YM155) studied by stimulated Raman, NMR and UV-Vis spectroscopies.
(PubMed, Spectrochim Acta A Mol Biomol Spectrosc)
- "We were unable to identify the 450 nm-absorbing product of the degradation neither by NMR nor stimulated Raman, yet our studies pointed at imidazole-linked methyl as being associated with the YM155 degradation. The alkaline degradation of YM155 could be related to its mechanism of action - binding to DNA in mitochondria with pH values above 8."
Journal • Oncology
July 17, 2025
Identification of Prognostic Biomarkers in Gene Expression Profile of Neuroblastoma Via Machine Learning.
(PubMed, Pediatr Discov)
- "Additionally, our findings revealed that these biomarkers are correlated to chemotherapy drugs, such as vincristine and cyclophosphamide. Furthermore, drug sensitivity analyses identified several candidate drugs, such as dactinomycin, bortezomib, docetaxel, and sepantronium bromide, that may hold therapeutic potential for NB treatment. This study offers novel insights to underlying NB prognosis and therapeutic targets and provides a foundation for developing personalized treatment strategies to improve clinical outcomes."
Biomarker • Journal • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • AURKA • BRCA1 • BRCA2 • CCNA2 • CHEK1 • E2F1 • MAD2L1 • PLK1 • RAD51 • RFC3
June 24, 2025
BIRC5 upregulation enhances DNMT3A-mutant T-ALL cell survival and pathogenesis.
(PubMed, Blood Neoplasia)
- "The prosurvival gene BIRC5 was upregulated in patients with DNMT3A-mutant T-ALL, and these cells were specifically sensitive to the Baculoviral IAP Repeat Containing 5 (BIRC5) inhibitor YM155. Genetic inhibition of BIRC5 in vivo lead to rapid depletion of DNMT3A-mutant T-ALL cells in patient-derived xenografts, positioning BIRC5 as a precision medicine target for these patients."
Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • BIRC5 • DNMT3A
April 28, 2025
Navitoclax, a Bcl-2/xL Inhibitor, and YM155, a Survivin Inhibitor, in Combination with Carboplatin, Effectively Inhibit Ovarian Cancer Tumor Growth.
(PubMed, Mol Cancer Ther)
- "Initial results showed that omipalisib, verteporfin, CA3, mitoxantrone, navitoclax, venetoclax, and YM155 had significant single-drug activity in either the ALDHlo or both the ALDHlo/ALDHhi cell populations...In vivo, the combination of navitoclax/YM155/carboplatin decreased ovarian cancer metastasis, decreased the percentage of ALDHhi ovarian cancer cells in tumors, and increased survival when compared with carboplatin treatment alone in xenograft models. Our results suggest that the combination of navitoclax/YM155/carboplatin has promise as a therapy for treating ovarian cancer."
Journal • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BCL2 • CA3
April 27, 2025
Serum Starvation-induced ROS Production Activates the ERK-AP-1-TfR1 Pathway to Up-regulate Survivin to Support Nasopharyngeal Carcinoma Cell Viability.
(PubMed, Cancer Genomics Proteomics)
- "The serum starvation-induced ROS-ERK-AP-1 axis is crucial for the up-regulation of TfR1, which contributes to survivin expression and ultimately sustains the viability of NPC cells."
Journal • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • BIRC5 • TFRC
March 26, 2025
Immune-associated genes as potential therapeutic targets in small cell lung cancer
(AACR 2025)
- "We identified AURKB, BIRC5, TOP2A, TYMS, PCNA, UBE2C, and AURKA genes as potential immune-related therapeutic targets for SCLC. In particular, high BIRC5 expression promotes SCLC progression and may influence the immune microenvironment of the tumor by affecting monocytes."
IO biomarker • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • AURKA • AURKB • GLI2 • PCNA • PD-L1 • TOP2A • TYMS • UBE2C
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