obatoclax (GX 15-070) / Teva - LARVOL DELTA

Non-apoptotic regulated cell death based prognostic risk model for colorectal cancer using machine learning guided two-step framework. (PubMed, Brief Bioinform) - "Biologically, the high-risk class showed enriched angiogenesis and EMT pathways, an immunosuppressive microenvironment, reduced immunotherapy response, and predicted increased sensitivity to CDK, MEK, and metabolic inhibitors, while the low-risk class showed increased sensitivity to the drug "Obatoclax Mesylate_1068". c-RCDI developed in this study using a novel two-step ML framework based on NARCD pathways showed robust predictive ability for CRC patients, with a potential for improving diagnosis and therapy."

Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor

Loss of ADAM15 prevents necroptosis induction by partial RIPK1 degradation due to enhanced TNF-R1 surface expression and basal caspase-8 activation. (PubMed, Cell Commun Signal) - "ADAM15 is a previously unknown regulator of necroptosis, likely due to its role in modulating intracellular organelle sorting processes. Its proteolytic activity and possible scaffolding capacity for recruiting adaptor molecules make it a veritable drug target. The activation or deactivation of ADAM15 may be exploited to modulate various disease conditions."

Journal • Inflammation • Targeted Protein Degradation • ADAM15 • CASP8 • FASLG • RIPK1 • TNFRSF1A

Chrono-Pharmacology for Cancer: Harnessing Circadian Regulations of the Cell Cycle and Immune Response Dynamics for Precision Therapy. (PubMed, ACS Pharmacol Transl Sci) - "We discussed some interesting examples, like HSP90 inhibitors (ganetespib), HDAC inhibitors (quisinostat), topoisomerase inhibitors (doxorubicin), and BCL-2 family antagonists (Obatoclax, TW-37), whose therapeutic activities are tightly regulated by circadian control over their molecular targets, pharmacokinetic processes, and downstream physiological pathways. Furthermore, the circadian influence extends to the tumor microenvironment and antitumor immunity, suggesting novel chrono-immunotherapy approaches. By putting together the molecular bases of these temporal dynamics, this review underscores the significant potential of chronotherapythe timed administration of drugs to improve cancer treatment by enhancing therapeutic indices and paving the way for personalized, temporally optimized oncology strategies."

Journal • Review • Oncology • Targeted Protein Degradation • ARNTL • BCL2 • BMAL1 • CDC37 • CDKN1A • FBXW7

Identification and Validation of Ferroptosis-Related Genes As Novel Prognosis Prediction Panel for Acute Myeloid Leukemia (ASH 2023) - "We found that bcl-2 inhibitor (Obatoclax Mesylate) and TKI (Gefitinib) may have less sensitivity in our high-risk group ( P<0. 05), while some unconventional drugs (paclitaxe, dactinomycin, camptothecin, irinotecan and vinorelbine) may benefit in patients with higher FRGs expression (Figure J). In summary, we identified and validated 10 FRGs signature to well predict the prognosis and drug sensitivity of AML. Based on our findings, appropriate combination of new drugs at the time of treatment may achieve unexpected therapeutic outcomes, but still need to go through further verification."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • GPX4 • LPIN1 • PSAT1 • SOCS1 • TP53

GX15-070 enhances niraparib efficacy in ovarian cancer by promoting a shift in Mcl1-mediated DNA repair pathway from HR to NHEJ. (PubMed, J Transl Med) - No abstract available

Journal • Oncology • Ovarian Cancer • Solid Tumor • MCL1

GX15-070 Boosts Niraparib Effectiveness in Ovarian Cancer (Bioengineer.org) - "Detailed analysis revealed that the combined treatment of GX15-070 and niraparib not only improves cell death rates in ovarian cancer models, but also alters gene expression profiles indicative of a shift in repair strategies."

Preclinical • Ovarian Cancer

Insights into the alteration of vaginal microbiota and metabolites in pregnant woman with preterm delivery: prospective cohort study. (PubMed, Front Cell Infect Microbiol) - "In addition, vaginal metabolomics-based LC-Orbitrap-MS/MS revealed that the contents of 2-Piperidone, Melphalan, N-acetylputrescine, Obatoclax, Eurostoside, Pregnanediol 3-O-glucuronide, O-Phospho-L-serine, 1-Kestose and N-arachidonylglycine were significantly decreased in the PrPG group compared with the PrTG group, while Acenocoumarol, Isopyrazam, Pentosidine, hexose, 7-Hydroxymitragynine, PE, Tamoxifen and 1-Deoxynojirimycin contents were significantly increased. These results suggest that specific bacterial species and metabolites may serve as potential biomarkers for preterm birth prediction, and approve the theoretical basis for the intervention of preterm birth."

Journal

Inhibition of anti-apoptotic Bcl-2 family members promotes synergistic cell death with ER stress inducers by disrupting autophagy in glioblastoma. (PubMed, Cell Death Discov) - "Under ER stress responses, GBM cells exerted an autophagy response to recover from the stress condition; however, obatoclax co-treatment disrupted the autophagy responses, particularly by disrupting autophagic cargo degradation. Our findings suggest that targeting Mcl-1 and Bcl-xL, coupled with ER-stress induction, could be a promising strategy for the treatment of GBM, highlighting the potential for combination therapies involving pan-Bcl-2 family inhibitors to overcome current limitations in the treatment of GBM."

IO biomarker • Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • ATF4 • BCL2 • BCL2L1 • CASP3 • CASP7

Targeting BCL-2 proteins as a Strategy Against Therapy Persistency in TNBC (EACR 2025) - "Resistant TNBC cell models (MDA-MB-231R, BT-549R) were generated using a cisplatin pulse-based strategy...A drug screening using BH3 mimetics drugs that directly induce apoptosis by inhibiting anti-apoptotic BCL-2 family members identified Obatoclax, a pan-inhibitor, as the most efficient compound to reduce proliferation in all tested TNBC cell lines, regardless of chemotherapy sensitivity... Our findings suggest that the simultaneous targeting of BCL2 anti-apoptotic members could represent a promising therapeutic approach for chemotherapy-resistant TNBC."

IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • Triple Negative Breast Cancer • BCL2 • BCL2L1 • HER-2 • MCL1

Screening of the Prodiginine Molecules as BH3-Mimetics against the Developed Bcl-2 Antiapoptotic Chemotherapeutic Resistance: A Molecular Docking and ADMET Study Supported by Molecular Dynamics Simulations. (PubMed, Curr Comput Aided Drug Des) - "Based on these results, butylcycloheptyl prodigiosin and prodigiosin-R2 could be more effective BH3 mimetics and should be further studied."

IO biomarker • Journal • Oncology • BCL2 • BCL2L1 • BCL2L2 • MCL1

Decoding the multifunctional potential of ursolic acid: antioxidant, antiproliferative, molecular dynamics, and biodegradability evaluations of a mangrove-derived terpenoid. (PubMed, J Comput Aided Mol Des) - "In the in silico studies, molecular docking of two ligands, Ursolic acid and Obatoclax, with the Bcl-B protein demonstrated notable binding affinities, with ΔG values of -5.8 kcal/mol and - 6.6 kcal/mol, respectively...Further, BIOWIN™ models indicated that the identified Ursolic Acid is biodegradable in an aerobic environment, underscoring its environmental compatibility. Deciphering the bioactivities of ursolic acid could uncover new therapeutic agents and enhance our understanding of its biodegradable environmental compatibility, revealing the source of already documented pharmacological compounds."

Journal • Oncology • BCL2L10

Obatoclax, a safe BH3-mimetic, is noninferior to neurotoxic oxaliplatin when combined with adenovirus to treat colorectal carcinoma (AACR 2025) - "OB-ADP treatment is noninferior to OX-AdV therapy in vitro for initiation of ICD. These results support using OB in an agnostic therapeutic vaccine in vivo, particularly due to its systemic injection capability."

Colorectal Cancer • Oncology • Solid Tumor • CALR • CD8 • DDIT3

The role of Bcl‑2 in controlling the transition between autophagy and apoptosis (Review). (PubMed, Mol Med Rep) - "Therapeutic strategies targeting Bcl‑2 (for example inhibitors such as venetoclax, navitoclax, obatoclax and combination therapies involving autophagy modulators) were evaluated for their potential efficacy. Future research should prioritize these areas and leverage advanced single‑cell technologies to elucidate the real‑time dynamics of Bcl‑2 in cell processes. The present review highlights the key role of Bcl‑2 in cell fate determination and highlights its potential as a therapeutic target, offering insight for the development of innovative treatments for cancer, neurodegenerative disorder and age‑related diseases."

Journal • Review • CNS Disorders • Oncology • Targeted Protein Degradation • BAX • BCL2 • BECN1

Inhibition of anti-apoptotic Bcl-2 family members leads to synergistic cell death with ER-stress inducers via disruption of autophagy in glioblastoma (AACR 2025) - "Eight GBM cell lines were treated with our in-house library compounds, revealing that a pan-Bcl-2 family inhibitor, obatoclax, effectively reduced cell viability across all GBM cell lines...In conclusion, our study suggests a unique model in which targeting anti-apoptotic Bcl-2 family proteins, such as Mcl-1 and Bcl-xL, coupled with ER-stress induction, demonstrates promising synergism and enhanced cell death in GBM. This highlights the potential of pan-Bcl-2 family inhibitors to overcome current therapeutic limitations in GBM, providing a novel foundation for future therapeutic approaches via the pro-apoptotic targeting method."

IO biomarker • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • ATF4 • BCL2 • BCL2L1 • CASP3 • CASP7

The pan-BH-3 mimetic, obatoclax, synergistically enhances cisplatin-induced apoptosis in oral squamous cell carcinoma through a mechanism that involves degradation of the pro-survival protein Mcl-1. (PubMed, Arch Oral Biol) - "Our study presents novel insights into the relationship between the Bcl-2 family and cisplatin efficacy in OSCC. It also demonstrates that targeted therapy with BH-3 mimetics, such as obatoclax, may represent a new strategy for OSCC therapy."

IO biomarker • Journal • Oncology • Oral Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ANXA5 • BCL2 • MCL1

Impact of Paracoccus sp. EGY7 carotenoids on triple-negative breast cancer cells: invitro study. (PubMed, AMB Express) - "Docking analysis indicated a strong affinity of zeaxanthin to BCL-2 (ΔG = -9.773241 kcal/mol) compared to obatoclax (ΔG = -7.419345 kcal/mol)...EGY7 carotenoids are a promising anticancer agent against MDA-MB-231 cells. They effectively promote apoptosis and prevent metastasis, crucial for disease advancement in cancer cells."

IO biomarker • Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BAX • BCL2

Relocating NSAIDs into the endoplasmic reticulum induces ER stress-mediated apoptosis in cancer cells. (PubMed, RSC Med Chem) - "Through screening the library in cancer cells, we identified a promising compound: an ibuprofen derivative conjugated with a dansyl group as a dual fluorescence tag and ER-targeting moiety. The resulting ER stress triggered autophagy by upregulating Beclin and LC3-II/LC3-I as autophagy markers, followed by apoptosis, culminating in significant cancer cell death, particularly when combined with bafilomycin A, 10-hydroxycamptothecin and obatoclax. This NSAID-based ER stress inducer provides a powerful tool for exploring the chemical biology of NSAIDs in the ER and holds great potential for advancing ER-targeted cancer therapies in combination with other anti-cancer drugs."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

Withania somnifera-derived phytochemicals as Bcl-B inhibitors in cancer therapy: A computational approach from byte to bench to bedside. (PubMed, Biochem Biophys Res Commun) - "The results demonstrated that the selected and prioritized phytochemicals, Withanolide L, Withanolide M, and Withanolide A display comparable efficacy to Obatoclax (CID: 11404337) and other known synthetic, semi-synthetic, and natural inhibitors of Bcl-2 family proteins. These findings establish a strong bench foundation for further experimental validation and bedside application, potentially offering an alternative natural approach to cancer therapy."

Journal • Infectious Disease • Oncology • BCL2 • BCL2L10

Elucidating molecular differences between cytoprotective and cytotoxic autophagy in lung cancer cell models (EORTC-NCI-AACR 2024) - "Particularly, the aim of this research is the characterization of the autophagy induced by cisplatin (CDDP) and obatoclax (OBX), inducers of cytoprotective and cytotoxic autophagy, respectively, as well as the analysis and comparison of molecular differences between them regarding the autophagic machinery. CDDP and OBX induce cytoprotective and cytotoxic autophagy, respectively, thus triggering different molecular changes that could potentially help differentiating the role of this process. Hence, these results may aid in the future to identify the role of autophagy in tumors and select the most appropriate therapeutic option for each patient."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

EXPLORING BLOOD-BRAIN BARRIER-PENETRATING DRUGS FOR THE IDENTIFICATION OF NOVEL THERAPIES IN GLIOBLASTOMA (SIOP 2024) - " Seven drugs: Obatoclax (Mesylate), COG1410, Fingolimod, Ozanimod, Lonafarnib, BMS-202 and Bazedoxifene (acetate) were screened out as potential candidates, with consistent efficacy against glioblastoma cells, providing promising avenues for standalone therapies in GBM or as enhancers of existing conventional chemotherapy regimens. This multi-faceted approach aims to develop personalized and effective treatment strategies for the challenging landscape of glioblastoma tumors. This work was supported by FAPESP grant numbers 2022/09037-3, National Council for Scientific and Technological Development (CNPq, MCTI, Brazil) grant number 406484/2022-8 (INCT BioOncoPed)"

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Prognostic model for hepatocellular carcinoma based on necroptosis-related genes and analysis of drug treatment responses. (PubMed, Heliyon) - "Notable, Bleomycin, Obatoclax. Mesylate, PF.562271, PF.02341066, QS11, X17. AAG, and Bl. D1870 exhibited significantly different sensitivities in different subtypes, providing references for clinical practice in HCC patients."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

An Innovative Multi-Omics Model Integrating Latent Alignment and Attention Mechanism for Drug Response Prediction. (PubMed, J Pers Med) - "High accuracy was achieved in predicting drug responses for piplartine and tenovin-6, while the accuracy was comparatively lower for mitomycin-C and obatoclax. In the interpretability case study, panobinostat exhibited the most effective predicted response, with a value of -4.895. We provide reliable insights for drug selection in personalized medicine by identifying crucial genetic factors influencing drug response."

Journal • Oncology

Identification of mitochondria-related gene biomarkers associated with immune infiltration in acute myocardial infarction. (PubMed, iScience) - "We obtained the potential drugs targeted at ALDH2, PMAIP1, and BCL2A1, such as disulfiram, obatoclax mesylate, and bortezomib. Quantitative reverse-transcription polymerase chain reaction further validated the expression of the MitoDEGs in the cell model of AMI. These findings reveal the potential role of MitoDEGs in AMI and provide new insights into risk stratification and individualized treatment of AMI patients."

Biomarker • Journal • Cardiovascular • Metabolic Disorders • Myocardial Infarction • ALDH2 • BCL2A1 • PMAIP1

Differential susceptibility of cells infected with defective and intact HIV proviruses to killing by obatoclax and other small molecules. (PubMed, AIDS) - "Obatoclax and other Bcl-2 inhibitors deserve further study in combination therapies aimed at reducing the intact HIV reservoir in order to achieve a functional cure and/or reduce HIV-associated immune activation."

Journal • Human Immunodeficiency Virus • Infectious Disease • IFNG

Frequent copy number gain of MCL1 is a therapeutic target for osteosarcoma (AACR 2024) - "The treatment for OS that combines surgery with chemotherapy, which consists of a four-drug combination of adriamycin (DOX), cisplatin (CDDP), high-dose methotrexate (MTX), and ifosfamide, was established in 1970s, and it is still used as a standard therapy...Herein, to explore the characteristic vulnerability in OS, molecular targeted drugs were screened against OS cell lines and patient-derived cells; obatoclax, a pan-BH3 mimetic, and a concomitant drug that enhances obatoclax-induced apoptosis, OSI906, a dual inhibitor of IGF1R and IR, were found...Thus, we elucidated the mechanism of action of drugs and their potential as a novel therapeutic strategy for approximately 50% of patients with OS. Moreover, a FISH analysis that can detect copy number gains of MCL1 in FFPE specimens from patients with OS was established to stratify patients eligible for this therapy."

IO biomarker • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • BCL2 • BCL2L1 • PIP5K1A