ABT-737 / AbbVie - LARVOL DELTA

BCL-2 family dysregulation in HTLV-1 and BLV pathogenesis and its implications for leukemogenesis and therapy. (PubMed, Mol Biol Rep) - "Small-molecule inhibitors such as ABT-737 and Navitoclax, kinase inhibitors targeting NF-κB (Nuclear Factor kappa-light-chain-enhancer of Activated B Cells) and JAK/STAT (Janus Kinase/Signal Transducer and Activator of Transcription) pathways, and natural compounds including fucoxanthin, peridinin, and thymoquinone have demonstrated the ability to overcome apoptosis resistance in preclinical models. Recent strategies combining MCL-1 inhibitors with antiretroviral therapy or immune checkpoint blockade further highlight the translational potential of targeting BCL-2 pathways. Collectively, the evidence positions the BCL-2 family as a critical determinant of deltaretroviral persistence and leukemogenesis, and as a promising therapeutic axis for the development of novel treatments for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) and BLV-associated leukosis."

Journal • Review • Adult T-Cell Leukemia-Lymphoma • B Cell Lymphoma • Genetic Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Oncology • BAX • BCL2 • BCL2L1 • BCL2L11 • BID

Identifying metabolic vulnerabilities of recurrent IDH1-R132H mutant glioma by high throughput screening (WFNOS 2025) - "Notable target pathways include folate metabolism and de novo thymidylate synthesis (methotrexate, raltitrexed, 5-FU), p97 AAA ATPase/VCP chaperone (CB-5083, ML240, eeyarestatin I), mevalonate pathway (Ro 48-8071 fumarate, atorvastatin calcium), and the BCL-2 family (Navitoclax, ABT-737). We are validating these drugs across a panel of patient-derived IDH-mutant gliomasphere models, and examining the combinatorial effects of these agents with vorasidenib and CDK4/6 inhibitors. Our results provide insight into important metabolic pathway dependencies in recurrent IDH1-R132H mutant gliomas that have targeting potential."

IO biomarker • Brain Cancer • Glioma • Oligodendroglioma • Solid Tumor • BCL2 • IDH1 • NAMPT

Impact of Cryopreservation and Cytokine Supplementation on ex vivo Drug Sensitivity in Primary AML Cells (DGHO 2025) - "Agents included venetoclax, ABT-737, a MCL-1 inhibitor, the PP2A activator FTY720, and the PP2A inhibitor LB100. Cryopreservation and cytokine-supplemented culture conditions can significantly impair drug response and signaling behavior in primary AML cells while addition of cytokines seem mandatory to allow growth of thawed PMBCs. Fresh samples cultured without cytokines appear to better preserve drug sensitivity but are not appropriate for long-term cultivation. Standardized approaches are beneficial to ensure reproducibility of functional testing in AML at this stage of research."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • ANXA5 • TP53

Multi‑omics analysis of Del20q reveals PHF20 haploinsufficiency and an HDAC2-centered epigenetic circuit in myeloid neoplasms (ASH 2025) - "Consistent with these roles,preliminary results in a PHF20 knockdown model in TF-1 cells showed accelerated proliferation andrendered the line cytokine-independent, functionally validating its leukemogenic potential.Transcriptome-wide analysis of del20q patient samples revealed an inverse correlation between PHF20and HDAC2 expression (r²=0.40, p=0.047); HDAC2 is the chief de-acetylase that removes H4K16ac, andloss of PHF20 appears to shift chromatin toward a heterochromatic, differentiation-blocked state.We screened six primary del20q AML samples and found marked BCL-2 dependence: venetoclax IC₅₀ 0.12µM versus 0.48 µM in diploid controls (ΔAUC –0.23, p=0.009) and a similar differential for ABT-737 (ΔAUC–0.21, p=0.012). In two tested samples, panobinostat showed promising activity (ΔAUC +0.17, p=0.17),suggesting that the PHF20–HDAC2 axis is therapeutically exploitable...These insights identify venetoclax-based regimens, potentiallypotentiated by HDAC..."

IO biomarker • Brain Cancer • Glioblastoma • Hematological Malignancies • Leukemia • Melanoma • Solid Tumor • BCL2 • CD34 • HDAC2 • TP53

Discovery of Novel PI3K/BRD4 Dual Inhibitors for Esophageal Cancer: Rational Design, Optimization, and Senescence-Inducing Mechanisms. (PubMed, J Med Chem) - "In vivo, 23 demonstrated anticancer efficacy comparable to that of the BKM120/JQ1 combination treatment in a KYSE450 xenograft mouse model. Significantly, the senolytic agent ABT737 enhanced the efficacy of compound 23 through the selective clearance of senescent cancer cells. Collectively, this work establishes 23 as a promising PI3K/BRD4 dual-targeting lead and supports senescence induction combined with senolytics as a novel strategy for esophageal cancer treatment."

Journal • Esophageal Cancer • Oncology • BRD4

Deciphering lactate/lactylation networks in AML: integrated scRNA-seq and transcriptomics reveal functions and prognostic model. (PubMed, BMC Cancer) - "Transcriptomic profiling indicated lactylation-associated immunosuppression (e.g., downregulated CXCL9/10-CXCR3 axis, enrichment of T cell exhaustion markers) and heightened in silico-predicted sensitivity to BCL-2/FGFR inhibitors (ABT-737/AZD4547) in high-risk patients. Collectively, integrated analyses uncovered lactate/lactylation-associated heterogeneity in AML. Our machine learning-based prognostic model predicts survival, therapeutic response, and drug sensitivity, suggesting a potential strategy for precision therapeutics in AML."

Biomarker • IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ARPP19 • BCL2 • CXCL9 • CXCR3 • IFI16

Integrative Analysis of Mitochondrial-Related Genes Reveals Diagnostic Biomarkers and Therapeutic Targets in Acute Pancreatitis. (PubMed, IET Syst Biol) - "Talniflumate and ABT-737 were predicted as potential therapeutic agents using the CMap and validated through molecular docking and 100-ns molecular dynamics simulations. This study establishes a mitochondria-related diagnostic model for AP and identifies candidate therapeutic agents, offering novel insights into the molecular pathogenesis and targeted intervention of AP."

Biomarker • Journal • Inflammation • Metabolic Disorders • Pancreatitis

[Retracted] ABT‑737, a Bcl‑2 family inhibitor, has a synergistic effect with apoptosis by inducing urothelial carcinoma cell necroptosis. (PubMed, Mol Med Rep) - "The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 23: 412, 2021; DOI: 10.3892/mmr.2021.12051]."

Journal • Oncology • Solid Tumor • Urothelial Cancer

HEPATIC STELLATE CELL-DERIVED HB-EGF SUPPRESSED HEPATOCYTE APOPTOSIS IN ACUTE LIVER INJURY (AASLD 2025) - "Liver injury was induced using lipopolysaccharide (LPS) and ABT-737, a Bcl-xL inhibitor... Depletion of HSCs exacerbates hepatocyte apoptosis during acute liver injury. Our findings suggest that HSC-derived HB-EGF plays a protective role by mitigating hepatocyte apoptosis and liver damage."

Fibrosis • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis • Liver Failure • ANXA5 • BCL2L1 • CASP3 • CASP7 • FAP • GFAP • HBEGF

DFNA5-DEPENDENT HEPATOCYTE DEATH PROMOTES TNF PRODUCTION IN KUPFFER CELLS AND CONTRIBUTES TO HEPATOCARCINOGENESIS (AASLD 2025) - " DFNA5 was silenced using siRNA in Huh7 and AML12 cells, and intrinsic apoptosis was induced with ABT-737, a Bcl-xL inhibitor...Kupffer cells were depleted using clodronate liposomes to assess their contribution to cytokine production... Dfna5 promotes secondary necrosis and Kupffer cell-mediated TNFα production, fueling inflammation and hepatocarcinogenesis. Targeting the Dfna5–TNFα axis may represent a novel therapeutic strategy for CLD-associated liver cancer."

Hepatocellular Cancer • Hepatology • Liver Cancer • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor • BCL2L1 • CASP3 • CASP7 • FASLG • GSDME • MCL1 • TNFA

The Combination of Ibrutinib with BH3 Mimetics or Dichloroacetate Is Effective in B-CLL. (PubMed, Cells) - "For this purpose, we combined this drug with the BH3 mimetics ABT-199 and ABT-737, which inhibit anti-apoptotic members of the Bcl-2 family, and with the PDK1 inhibitor dichloroacetate (DCA), respectively. Mechanistically, the expression of Bcl-2-family proteins was explored, exhibiting increases in pro-apoptotic, but also in anti-apoptotic, proteins upon ibrutinib treatment and a relative increase in the amount of the pro-apoptotic protein PUMA after treatment with DCA. Our data provides new insights into combined therapies with ibrutinib for CLL, which further expands our knowledge and the potential of this drug for cancer treatment."

IO biomarker • Journal • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • BCL2 • BCL2L1 • MCL1

Role of Bcl-2 Family Anti-apoptosis Inhibition in Overcoming Therapeutic Resistance in Prostate Cancer: A Systematic Review. (PubMed, Crit Rev Oncol Hematol) - "This systematic review demonstrates that inhibition of Bcl-2 family anti-apoptotic proteins can potentiate the efficacy of standard treatments for prostate cancer. These findings provide a compelling rationale for further research into targeted combination therapies to overcome therapeutic resistance in PCa."

IO biomarker • Journal • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BCL2 • BCL2L1

Senolytic Potential of Fisetin and ABT Compounds in Dermal Fibroblasts (ESDR 2025) - "This study aimed to identify effective senolytics for dermal aging treatment by comparing the senolytic properties of several known compounds—including Dasatinib, Fisetin, Quercetin, Navitoclax (ABT263), ABT737, and Resveratrol—in senescent human dermal fibroblasts (HDFs)...The SASP-driven effects on normal cells were effectively mitigated. Overall, all tested compounds demonstrated senolytic activity, but Fisetin, ABT263, and ABT737 exhibited the highest efficacy in HDFs, highlighting their potential as promising candidates for future studies on dermal aging interventions."

IL6

Prognostic significance of angiogenesis-associated molecules and Immunologic characteristic in elderly patients with acute myeloid leukemia. (PubMed, Ann Hematol) - "We have constructed an angiogenesis-related gene prognostic signature that enriches the prognostic assessment system for AML and provides novel therapeutic directions for this disease."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • EGLN1 • FKBP5 • FOXP1

Single-cell and spatial transcriptomics map senescent vascular cells in arterial remodeling during atherosclerosis in mice. (PubMed, Nat Aging) - "Using the SenMayo and CellAge gene sets, we identified four clusters of vascular smooth muscle cells (VSMCs), fibroblasts and T cells enriched in features of senescence, which were reduced upon treatment with the senolytic agent ABT-737...We validated the enrichment of these mRNAs in senescence by using spatial transcriptomics in a second mouse model of atherosclerosis and senolysis (Ldlr-/-; p16-3MR), as well as by analyzing in vitro models of human VSMC senescence. Our results uncover a vascular-specific transcriptomic signature of senescence that may be exploited for tracking and treating age-related vascular diseases."

Journal • Preclinical • Atherosclerosis • Cardiovascular • PCSK9 • SPP1 • TNFRSF11B

Bim and Mcl-1 Coordinate NVP-BEZ235-induced Renal Cell Carcinoma Cell Apoptosis. (PubMed, Arch Biochem Biophys) - "Bcl-2 inhibitor ABT-737 and Mcl-1 inhibitor AZD5991 predisposed NVP-BEZ235-treated cells to transform into the apoptotic phenotype. PI3K inhibitor LY294002 and Stat3 inhibitor AG490 duplicated the sensitized actions towards NVP-BEZ235...Data of in vivo tumor-bearing studies further revealed a better anti-tumor potential in the combination treatment of NVP-BEZ235 and MEK/ERK inhibitors without obvious toxicity. Our findings suggest that the feedback activation of pro-survival machinery is likely to be the main cause of cancer cells being refractory to NVP-BEZ235, and a combination treatment is a feasible strategy to sensitize cancer cell responses."

IO biomarker • Journal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Targeted Protein Degradation • BCL2L11 • MCL1

Integrated single-cell and bulk RNA dequencing to identify and validate prognostic genes related to T Cell senescence in acute myeloid leukemia. (PubMed, Front Bioinform) - "Prognostic genes showed strong binding activity to target drugs (IGF1R and ABT737)...CALR, CDK6, HOXA9, and PARP1 predicted disease progression and prognosis in patients with AML. Based on these, we developed and validated a new AML risk model with great potential for predicting patients' prognosis and survival."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CALR • CDK6 • HOXA9 • PARP1

Senescent Microglia Mediate Neuroinflammation-Induced Cognitive Dysfunction by Selective Elimination of Excitatory Synapses in the Hippocampal CA1. (PubMed, Aging Cell) - "A senolytic by ABT-737 treatment alleviated the production of senescence-associated secretory phenotypes, the accumulation of senescent microglia, and the microglial hyperphagocytosis of excitatory synapses following LPS exposures. This treatment also restored reduced excitatory synaptic transmission, impaired long-term potentiation, and cognitive function in the model. These results indicate that reducing senescent microglia may potentially serve as a therapeutic approach to prevent neuroinflammation-related cognitive dysfunction."

Journal • CNS Disorders • Cognitive Disorders • Inflammation • CDKN2A

Proffered Paper: Targeting senescent macrophages inhibits metastatic dissemination in adrenocortical cancer (EACR 2025) - "These findings indicate that senescent immunosuppressive macrophages play a key role in metastatic dissemination in ACC. Their targeted clearance using senolytic therapy presents a promising therapeutic strategy for combating metastatic progression in this aggressive malignancy."

Metastases • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CDKN1B • PTPRC • ZNRF3

Overcoming Gemcitabine Resistance in MDA-MB-231 Cells: A Synergistic Approach Using ABT-737 and NVP-BEZ235 Dual Inhibition of PI3K/mTOR (EACR 2025) - "Our results suggest that the combination of ABT-737 and NVP-BEZ235 is a promising therapeutic strategy for overcoming Gemcitabine resistance in TNBC. This combinational approach enhances apoptosis and inhibits cell proliferation and migration by targeting both the PI3K/mTOR pathway and Bcl-2 family proteins. Further studies are needed to assess the potential of this strategy for GEM-resistant TNBC."

IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CASP3 • ER • HER-2 • MCL1

Targeting Cellular Senescence to Enhance Human Endometrial Stromal Cell Decidualization and Inhibit Their Migration. (PubMed, Biomolecules) - "Although non-flavonoids exhibited notable cytotoxicity, dasatinib, but neither ABT-737 nor navitoclax, enhanced decidualization. Furthermore, flavonoid-senolytics and dasatinib consistently eliminated senescent eSCs. These findings support future studies to assess the therapeutic potential of in vivo supplementation with flavonoid senolytics on eSC function using menstrual effluent."

Journal • Endometriosis • Gynecology • Infertility • Sexual Disorders • Women's Health • TP53

The role of Sine Oculis Homeobox Homolog 2 in colon Cancer: Insights into prognosis, immune regulation, and therapeutic implications. (PubMed, Biochem Biophys Res Commun) - "Additionally, ABT737 was found to sensitize tumor immunotherapy in the context of SIX2...It could reduce the infiltration of CD163+ tumor-associated macrophages but without significantly increasing the infiltration of CD8+ T cells. Our findings suggest that SIX2 is a potential key player in CC, offering insights into future research and the development of targeted therapies."

IO biomarker • Journal • Colon Cancer • Colorectal Cancer • Inflammatory Arthritis • Oncology • Solid Tumor • CD163 • CD8 • TGFB1

Prognostic and immunological role of RHEBL1 in pan-cancer: a target for survival and immunotherapy. (PubMed, Discov Oncol) - "Pan-cancer samples suggested that high RHEBL1 expression facilitates TAM infiltration and is correlated with tumour immunosuppressive status (TCGA). High expression of RHEBL1 may benefit from the therapy of 5-FU, ABT737, Afuresertib, AGI-5198, AGI-6780, and Alisertib."

IO biomarker • Journal • Pan tumor • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • CD8 • RHEB

Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. (PubMed, J Integr Med) - "Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; Epub ahead of print."

Journal • Gastric Adenocarcinoma • Gastric Cancer • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Solid Tumor • Targeted Protein Degradation • PMAIP1

Anti-tumor Effects of Curcumin and ABT-737 in Combination Therapy for Glioblastoma in Vivo. (PubMed, Int J Mol Cell Med) - "In conclusion, curcumin has the ability to inhibit the cell proliferation and migration, and activate the intrinsic pathway of apoptosis. Moreover, it can enhance the sensitivity of glioblastoma cells to ABT-737 by suppressing the expression of Mcl-1."

IO biomarker • Journal • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • BCL2 • CASP3 • MCL1