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

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

An integrated framework for prognosis prediction and drug response modeling in colorectal liver metastasis drug discovery. (PubMed, J Transl Med) - "This study highlights the significance of developing specialized prognostication approaches and investigating effective therapeutic drugs for patients with CRLM. The application of a deep learning drug response model provides a new drug discovery strategy for translational medicine in precision oncology."

IO biomarker • Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Molecular dynamics simulations assisted investigation of phytochemicals as potential lead candidates against anti-apoptotic Bcl-B protein. (PubMed, J Biomol Struct Dyn) - "The identified molecules also exhibited specific interactions with critical amino acid residues of the binding cleft, highlighting their potential as lead candidates. Finally, molecular dynamics simulations and MM/PBSA based binding free energy analysis revealed that Enterolactone (CID_114739) and Piperine (CID_638024) molecules were on par with Obatoclax (CID_11404337), which is a known inhibitor of the Bcl-2 family proteins.Communicated by Ramaswamy H. Sarma."

Journal • Oncology • BCL2 • BCL2L10

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

Bcl-2 Antagonist Obatoclax Reactivates Latent HIV-1 via the NF-κB Pathway and Induces Latent Reservoir Cell Apoptosis in Latently Infected Cells. (PubMed, ACS Infect Dis) - "In addition, obatoclax exhibited potent anti-HIV-1 activity on target cells. The abilities to reactivate latent HIV-1 reservoirs, inhibit HIV-1 infection, and induce HIV-1 latent cell apoptosis make obatoclax worth investigating for development as an ideal LRA for use in the "shock and kill" approach."

Journal • Human Immunodeficiency Virus • Infectious Disease • BCL2 • CASP8 • CD4

Development of novel cytoprotective small compounds inhibiting mitochondria-dependent cell death. (PubMed, iScience) - "M109S inhibited ABT-737-induced apoptosis both in Bax-only and Bak-only mouse embryonic fibroblasts. M109S also inhibited apoptosis induced by staurosporine, etoposide, and obatoclax...M109S is a novel small molecule protecting cells from mitochondria-dependent apoptosis both in vitro and in vivo. M109S has the potential to become a research tool for studying cell death mechanisms and to develop therapeutics targeting mitochondria-dependent cell death pathway."

Journal • Ophthalmology

Obatoclax Rescues FUS-ALS Phenotypes in iPSC-Derived Neurons by Inducing Autophagy. (PubMed, Cells) - "Proteomics data suggest that obatoclax protects neurons via multiple mechanisms. Thus, obatoclax is a candidate for repurposing as a possible ALS therapeutic and, potentially, for other age-associated disorders linked to defects in protein homeostasis."

IO biomarker • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • BCL2 • BECN1 • FUS

Atg5 knockout induces alternative autophagy via the downregulation of Akt expression. (PubMed, Toxicol Res) - "Additionally, transformed cells, regardless of their Atg5 KO status, were more sensitive to autophagy inhibitors (SBI-0206965, chloroquine, and obatoclax) than the untransformed NIH 3T3 cells, suggesting that the transformed cells are more autophagy-dependent than the normal cells. Therefore, our study provides evidence that alternative autophagy may contribute to tumorigenesis in cells with an impaired Atg5-dependent autophagy pathway. The online version contains supplementary material available at 10.1007/s43188-023-00191-3."

Journal • Oncology • ATG5

Differential susceptibility of cells infected with defective and intact proviruses to HIV-selective cell killing by small molecule therapies (IAS-HIV 2023) - " We tested drugs currently in clinical use or human trials, including interferon alpha2A, interferon gamma, acitretin (RIG-I inducer), GS-9620/vesatolimod (TLR7 agonist), nivolumab (PD-1 blocker), auranofin (p53 modulator), obatoclax (Bcl-2 inhibitor), FX-1 (Bcl-6 inhibitor), bortezomib (proteasome inhibitor), birinapant (IAP inhibitor), and INK128/sapanisertib (mTOR[c]1/2 inhibitor)... Several drugs induced selective ex vivo depletion of cells with intact proviruses (obatoclax, possibly auranofin, INK128, and bortezomib) or defective proviruses (vesatolimod). Their distinct modes of action on cell death/survival and innate immune response provide a strong rationale to compare the effects of drug combinations ex vivo and in animal or human trials."

Human Immunodeficiency Virus • Infectious Disease • BCL6 • IFNA1 • IFNG • IL2

Screening of predicted synergistic multi-target therapies in glioblastoma identifies new treatment strategies. (PubMed, Neurooncol Adv) - "The highest synergies were observed in the drug combinations Lapatinib with Thapsigargin and Lapatinib with Obatoclax Mesylate, both targeting epidermal growth factor receptor and affecting the apoptosis pathway. To further elaborate on the apoptosis cascade, we investigated other, more clinically relevant, apoptosis inducers and observed a strong synergistic effect while combining Venetoclax (BCL targeting) and AZD5991 (MCL1 targeting). Overall, we have identified via a high-throughput drug screening several new treatment strategies for GBM. Moreover, an exceptionally strong synergistic interaction was discovered between kinase targeting and apoptosis induction which is suitable for further clinical evaluation as multi-targeted combination therapy."

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