sepantronium bromide (PC-002) / Astellas, Cothera Biosci - LARVOL DELTA

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

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

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

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

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

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

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

Survivin degrader 7I14 synergizes with docetaxel in castration-resistant prostate cancer by disrupting survivin dimerization and inducing its proteasome-dependent degradation (AACR 2025) - "In a PC-3 xenograft model, 7I14 at 15 mg/kg administered via IP twice/week effectively suppressed tumor growth and enhanced docetaxel's effects by degrading survivin, with no added toxicity, as assessed by body weight, white blood cell counts, and hemoglobin levels. Thus, targeting survivin's dimerization domain is a promising strategy for its degradation, and 7I10 and 7I14 have potential as single agents or in combination with docetaxel for treating metastatic CRPC."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BIRC5 • CASP3 • CASP9

Navitoclax, a Bcl-2/xL inhibitor, and YM155, a survivin inhibitor, in combination with carboplatin effectively inhibit ovarian cancer tumor growth (AACR 2025) - "Initial results showed that Omipalisib, Verteporfin, CA3, Mitoxantrone, Navitoclax, Venetoclax and YM155 had significant single drug activity in either the ALDH low or both the ALDH low/high cell populations... Our results suggest that the combination of Navitoclax/YM155/carboplatin has promise as a therapy for the treatment of OvCa."

Combination therapy • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BCL2 • CA3

Synthesis, Antiproliferative Activity, and Molecular Simulation Study of Novel Nootkatone Derivatives Containing Pyrazole-amide Moiety. (PubMed, Chem Biodivers) - "Furthermore, the possible interaction mode of compound 4r with Survivin protein was probed by molecular docking and found that compound 4r shared similar binding patterns with that of Survivin protein inhibitors YM155 and NSC80467. The work can bring new inspiration to the exploration of new types of anticancer drugs."

Journal • Breast Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Broad-spectrum ubiquitin-specific protease inhibition as a mechanism for the cytotoxicity of YM155 in cancers. (PubMed, Sci Rep) - "In cancers driven by these proteins, YM155 induces profound cell apoptosis and markedly inhibits tumor growth in xenograft models. Together, these findings demonstrate that YM155 is a broad-spectrum USP inhibitor, and a potential drug candidate for cancers which depend on hyper-active oncogenic proteins that are regulated by the ubiquitin-proteasome pathway."

Journal • Oncology • Targeted Protein Degradation • MYC • NOTCH1

STD NMR Epitope Perturbation by Mutation Unveils the Mechanism of YM155 as an Arginine-Glycosyltransferases Inhibitor Effective in Treating Enteropathogenic Diseases. (PubMed, JACS Au) - "Finally, we also demonstrate that YM155 effectively treats enteropathogenic diseases in a mouse model, highlighting its therapeutic potential. Overall, our data suggest that this compound can be repurposed to not only treat cancer but also infectious diseases."

Journal • Infectious Disease • Oncology

Patient-derived tumoroid xenograft models for preclinical validation of therapeutics for pleural mesothelioma (ELCC 2025) - "Pilot studies evaluated the therapeutic effects of romidepsin, a histone deacetylase inhibitor, and sepantronium bromide (YM155), a survivin inhibitor, compared to cisplatin-pemetrexed, the current standard of care. We demonstrated the feasibility of tumoroid xenograft models for preclinical validation of PM therapies. The models accurately reflect disease heterogeneity and provide a robust platform for drug testing. Our initial data suggest survivin as a novel target, warranting further studies to confirm the therapeutic efficacy of YM155."

Preclinical • Lung Cancer • Oncology • Solid Tumor • VIM

Survivin (BIRC5) is Highly expressed in Glioblastoma Tissue and Modulates Stiffness-Mediated Proliferation of Glioblastoma Cells (USCAP 2025) - "These results show a crucial role of Survivin in stiffness-mediated proliferation of glioblastoma cells in vitro and in vivo. Targeting Survivin and its signaling pathways could be promising approach for developing mechanosensitive therapeutic treatments for GBM."

Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • BIRC5 • CCND1

Potency and selectivity of a novel pan-RAS inhibitor in 3D bioprinted organoid tumor models. (PubMed, bioRxiv) - "ADT-007 exhibited high potency and selectivity in KRAS-mutant BOTs, reducing tumor burdens >30% at nanomolar concentrations, and demonstrated superior selectivity over bortezomib and YM155 with minimal cytotoxicity in RAS-WT BOTs...This study also underscores the translational utility of 3D BOT models for preclinical drug response assessment. Further validation in patient-derived BOTs is necessary to evaluate potential of ADT-007 in clinical settings."

Journal • Preclinical • Colorectal Cancer • Oncology • Solid Tumor • KRAS

Integrative analysis of cuproptosis-related lncRNAs for prognostic risk assessment and tumor immune microenvironment evaluation in laryngeal squamous cell carcinoma. (PubMed, Int J Biol Macromol) - "GIHCG's competing endogenous RNAs (ceRNA) and co-expression networks (CEN) were established, revealing sensitivity to drugs like BMS-509744, YM155, and KU-55933...Moreover, METTL16-mediated m6A methylation regulates GIHCG expression. In conclusion, this study successfully established a prognostic model comprising nine cuproptosis-related lncRNAs, accurately predicting LSCC prognosis, and highlighted the crucial role of GIHCG as a novel nucleic acid biomarker in regulating LSCC progression."

Journal • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • METTL16 • SNHG12

Survivin in cardiovascular diseases and its therapeutic potential. (PubMed, Vascul Pharmacol) - "Furthermore, given the limited research on survivin as a therapeutic target for CVDs, potential clinical avenues, including YM155 (a survivin inhibitor) or adenoviral, adeno-associated, and lentiviral vectors, are also discussed. Overall, this review highlights survivin as a promising target for mitigating the detrimental effects of CVDs and to provide new perspectives to advance research on the intervention of CVDs and associated pathologies."

Journal • Review • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Myocardial Infarction • Oncology • BIRC5

Overexpression pattern, function, and clinical value of proteasome 26S subunit non-ATPase 6 in hepatocellular carcinoma. (PubMed, World J Clin Oncol) - "This study was the first to discover that PSMD6 was overexpressed in HCC tissues. PSMD6 is essential for the growth of HCC cells and may be involved in ribosome biogenesis and RNA splicing."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Revolutionizing prognosis: Introducing cell death index (CDI) as a powerful prognostic tool for CSCC patients. (PubMed, Environ Toxicol) - "This investigation constructed a novel effective prognostic indicator of CDI in patients with CSCC and identified potential genes associated with cell death that could be targeted for prognosis and treatment of CSCC."

Journal • Cervical Cancer • Cervical Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

A generative deep neural network for pan-digestive tract cancer survival analysis. (PubMed, BioData Min) - "The experiment indicate that GDEC outperforms better than other deep-learning-based methods, and the interpretable algorithm can select biologically significant genes and potential drugs for DTC treatment."

IO biomarker • Journal • Gastrointestinal Cancer • Infectious Disease • Oncology

PC002-01: Sepantronium Bromide for the Treatment of High-grade B-cell Lymphoma (clinicaltrials.gov) - P2 | N=14 | Active, not recruiting | Sponsor: Cothera Bioscience, Inc | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2024 ➔ Jun 2025 | Trial primary completion date: Sep 2023 ➔ Mar 2025

Enrollment closed • Trial completion date • Trial primary completion date • B Cell Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • MYC

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

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

BCL2 Protein Progressively Declines during Robust CLL Clonal Expansion: Potential Impact on Venetoclax Clinical Efficacy and Insights on Mechanism. (PubMed, Lymphatics) - "Findings that robust CLL cycling associates with progressively decreasing BCL2 protein that directly correlates with decreasing venetoclax susceptibility, combined with past findings that these cycling cells have the greatest potential for activation-induced cytosine deaminase (AICDA)-driven mutations, suggest that venetoclax treatment should be accompanied by modalities that selectively target the cycling compartment without eliciting further mutations. The employment of survivin inhibitors might be such an approach."

IO biomarker • Journal • Chronic Lymphocytic Leukemia • AICDA • BCL2 • BIRC5 • IL15 • MCL1 • MIR15A • MIR16 • MIR16-1 • STAT5 • TLR9

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