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

A Novel Cell-Based High-Throughput Screening Model for Inhibitors Targeting Influenza Virus Hemagglutinin-α-2,6-Sialic Acid Interaction. (PubMed, Biomolecules) - "Screening 10,000 compounds identified Obatoclax Mesylate and Ethylparaben as primary hits...Molecular docking confirmed their binding to type A H1N1, H3N2, and B/Victoria HA proteins, while ADMET predictions highlighted specific structural optimization needs to mitigate toxicity. In conclusion, this subtype-independent, highly specific high-throughput screening (HTS) model provides an efficient and reliable platform for early-stage influenza drug discovery and lead compound development."

Journal • Infectious Disease • Influenza • Respiratory Diseases • ST6GAL1

Targeting protein-protein interactions in the BCL-2 family: opportunities for precision oncology. (PubMed, Clin Transl Oncol) - "Furthermore, we critically discuss the active role of the BCL-2 family in modulating apoptosis and evaluate recent advances in the development of BH3 mimetics (Venetoclax (ABT-199), Navitoclax (ABT-263), Obatoclax (GX15-070)) and other BCL-2-targeted therapies. The single- and combined therapy with Venetoclax, a selective BCL-2 BH3 mimetic, has demonstrated higher efficacy and improved safety compared with conventional therapies and has been successfully applied across distinct cancer types. Finally, we discuss current challenges, including resistance mechanisms and treatment-related toxicities, and outline future directions focusing on biomarker-guided patient stratification and next-generation BCL-2-targeted therapeutics."

IO biomarker • Journal • Review • B Cell Lymphoma • Lymphoma • Oncology • BCL2 • MCL1

Identification and Validation of a Lipid Metabolism-Related Gene Signature for Predicting Prognosis and Immunotherapy Response in Oral Squamous Cell Carcinoma. (PubMed, Metabolites) - "Notably, several drugs (e.g., obatoclax mesylate) showed significant efficacy in the high-risk group, representing promising therapeutic candidates. This study reveals that the LMRG signature could serve as a valuable tool for prognosis assessment, risk stratification, and therapy guidance in OSCC."

Gene Signature • IO biomarker • Journal • Tumor mutational burden • Metabolic Disorders • Oncology • Oral Cancer • Squamous Cell Carcinoma • CD8 • TMB

Construction of a Vasculogenic Mimicry-related RiskScore Model to Assess Patient Prognosis and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma. (PubMed, Curr Gene Ther) - "The VM-related RiskScore we developed serves as a reliable prognostic and predictive tool, providing valuable guidance for risk stratification and immunotherapy decision-making in HNSC patients."

IO biomarker • Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • COL8A2 • DCHS1 • FMOD • HTRA1 • TNFAIP6

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

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

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

Evaluation of Drugs with Selective Inhibitors Targeting the Anti-Apoptotic Protein B-cell Lymphoma 2 (BCL-2) with Pro-Apoptotic and Antineoplastic Activities in Grade IV Glioblastoma. (PubMed, Turk Neurosurg) - "Venetoclax, navitoclax, and obatoclax represented significant advances in apoptosis-targeted therapy, with venetoclax emerging as the most clinically successful agent. However, resistance mechanisms and side effects were significant challenges, necessitating further preclinical and clinical studies to optimize the therapeutic potential of these agents."

Journal • Acute Myelogenous Leukemia • B Cell Lymphoma • Brain Cancer • Chronic Lymphocytic Leukemia • Glioblastoma • Hematological Disorders • Leukemia • Lymphoma • Oncology • Solid Tumor • Thrombocytopenia • BCL2 • BCL2L1 • MCL1

AI-Driven Acceleration of Fluorescence Probe Discovery. (PubMed, Adv Sci (Weinh)) - "Focusing on three clinically relevant targets (tau, BCL-2, and TDP-43), we validated AI-identified candidates and discovered PE859, obatoclax, and B3, which supported applications in spectral analysis, drug screening, pathological labeling, cell imaging, and ex vivo tumor imaging...With improved photophysical properties, 859-2 enabled in vivo two-photon imaging of tau pathology in transgenic mice. This hybrid AI-bioassay strategy substantially broadens the accessible scaffold landscape for designing target-specific fluorescence probes and provides a scalable, efficient, and cost-effective framework for next-generation probe discovery."

Journal • Oncology • BCL2 • TARDBP

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

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

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