ABT-737 / AbbVie - LARVOL DELTA

Overcoming ABT-737 resistance in triple-negative breast cancer: C-phycocyanin-mediated myeloid cell leukemia-1 downregulation enhances apoptotic sensitivity. (PubMed, Mol Biol Rep) - "C-Phycocyanin synergistically enhances ABT-737 efficacy in MDA-MB-468 TNBC cells by suppressing compensatory Mcl-1 upregulation and modulating apoptotic regulators. This natural-product-based combination offers a promising strategy to overcome BH3-mimetic resistance, although further validation in additional TNBC cell lines is warranted."

IO biomarker • Journal • Breast Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • Triple Negative Breast Cancer • BCL2 • CASP3 • MCL1 • TP53

Metabolism pathway-based subtyping in pancreatic adenocarcinoma: an integrated study by bulk RNA-sequence and machine learning algorithms. (PubMed, Int J Surg) - "Drug sensitivity analysis showed that the high-risk group was more sensitive to AZD6244, ABT737, and other drugs. This study stratified patients with PAAD into three subgroups based on metabolic pathways and prognostic information, revealing significant differences in clinical outcomes, immune characteristics, and genetic mutations. The robust RS model developed from these findings demonstrated strong predictive power for patient survival and identified promising therapeutic strategies, providing valuable insights for advancing precision medicine in PAAD."

Journal • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

Assessing BCL2 paralog specificity using scyllatoxin-based BH3 domain mimetics | Poster Board #1065 (ACS-Fall 2026) - "Furthermore, ScTx-Bax mimetics facilitated cyt c release from intact mitochondria and, in some cases, outperformed isolated Bax-BH3 domain peptides and ABT-737 at disrupting AAP:ePAP interactions. In summary, our findings demonstrate that the ScTx-Bax peptide is a robust molecular scaffold for probing the molecular nature of AAP:ePAP interactions and developing selective BH3 mimetics that target discrete AAPs."

B Cell Lymphoma • Lymphoma • BCL2 • BCL2L1

Effects of BCL-2 and MCL-1 Inhibition on Apoptotic and Transcriptional Profiles in Acute Myeloid Leukemia. (PubMed, Medicina (Kaunas)) - "We studied the effects of the BCL-2 inhibitor ABT-737, the MCL-1 inhibitor S63845, and their combination on AML cell lines and primary AML patient cells. BCL-2 and MCL-1 inhibition, alone or in combination, induced apoptosis and altered the expression of epigenetic regulators and oncogenes in AML cell lines and primary patient cells, with no consistent advantage of combined treatment over single agents. BCL-2/MCL-1 inhibition remains a promising approach for AML, and further work should clarify which patients or disease subtypes are most likely to benefit from combined versus single-agent treatment."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • CASP9 • DNMT1 • HDAC1 • SUZ12 • WT1

Integrating Bulk and Single-Cell RNA Sequencing to Identify Prognostic Genes Associated with Adaptive Immunity and the Tumor Microenvironment in Cholangiocarcinoma for Risk Model Construction. (PubMed, Immunobiology) - "An AIR-related gene signature stratifies CCA prognosis by reflecting TME composition rather than tumor-intrinsic drivers, highlighting immune cell-centric mechanisms and intratumoral microbiota. The nomogram may aid prognostic stratification in research settings."

Biomarker • IO biomarker • Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Oral Cancer • Solid Tumor • C17orf99 • C1QA • CD55 • CD74 • CD8 • CD80 • ZAP70

A bovine in vitro platform improves species comparability of mitochondrial apoptosis drug-response readouts. (PubMed, Arch Toxicol) - "Functionally, bovine BFH12 cells showed minimal apoptotic response to the BH3 mimetic ABT-737 as a single agent, while responding robustly to doxorubicin and actinomycin D, as assessed by cytochrome c release, caspase processing and activity, and Annexin V/PI cytometry. These findings identify species-dependent regulation of BAX/BAK retrotranslocation and OMM assembly states as a baseline variable that shapes intrinsic-apoptosis pharmacodynamics. Incorporating bovine systems as a complementary non-rodent in vitro platform may improve model selection and pharmacodynamic readouts for compounds expected to engage mitochondrial apoptosis, thereby reducing avoidable translational misclassification in apoptosis-focused pipelines."

Journal • Preclinical • ANXA5 • BAX • BCL2

CFHR5 promotes colorectal cancer by upregulating COX4I2 to inhibit ferroptosis. (PubMed, Ann Med Surg (Lond)) - "Drug sensitivity analysis suggested that CFHR5 downregulation increased CRC cell sensitivity to ABT-737, while molecular docking revealed a strong binding affinity between CFHR5 and ABT-737 (binding energy: -9.4 kcal/mol). Our study demonstrates that CFHR5 promotes CRC progression by upregulating COX4I2 and inhibiting ferroptosis. These findings highlight CFHR5 as a promising biomarker and therapeutic target for CRC, warranting further validation in experimental and preclinical models."

Journal • Colorectal Cancer • Oncology • Solid Tumor

Brain-Derived Neurotrophic Factor Enhances Megakaryocyte Maturation and Promotes Proplatelet Formation (ISTH 2026) - "Apoptosis was evaluated by Annexin V binding and caspase-3/5 activation at days 9, 12, and 14, and following acute treatment of day-9 megakaryocytes with the BCL-2 family inhibitor ABT-737...Together with active BDNF internalization and genetic validation by CRISPR-Cas9, these data identify BDNF as a key regulator of platelet production. Page 2 DOI*10.1016/j.rpth.2026.105130"

IO biomarker • Cardiovascular • ANXA5 • BDNF • CASP3 • CD34

UPR/ATF4/Noxa pathway over-activation through SERCA2 inhibition or ONC201 treatment combined with ABT-737 triggers apoptosis in chemoresistant ovarian cancer cells and patient-derived tumor organoids (EACR 2026) - "Introduction: Ovarian cancer has a poor clinical prognosis due to chemoresistance following carboplatin/paclitaxel treatment...Material and The platinum-resistant cell line, OAW42-R, the HGSOC ovarian cell line OVCAR3 and patient-derived tumor organoids models (PDTO) were treated with anti-SERCA2 strategies (thapsigargin and siRNA targeting SERCA2) in presence of ABT-737.Result and Anti-SERCA2 strategies reverted the BCL-2 family member expression ratio in favour of pro-apoptotic proteins... Collectively, our study highlights that ABT 737, through BCL-xL inhibition and synergy with ER stress inducers, triggers ovarian cancer death, offering promising strategies for overcoming chemoresistance in relapsed ovarian cancer."

Clinical • IO biomarker • Oncology • Ovarian Cancer • Solid Tumor • ATF4 • BCL2 • BCL2L1

Mechanistic Study of the Antidepressant Agomelatine in Modulating STING Activity During the Pathogenesis of Systemic Lupus Erythematosus (EULAR 2026) - "Peritoneal macrophages (PEMs) were were stimulated with various stimuli, including lipopolysaccharide (LPS), interferon-stimulatory DNA (ISD), herpes simplex virus (HSV), cyclic GMP-AMP (cGAMP), ABT-737 + QVD-OPh, at different time points (0 h, 3 h, 6 h)...RT-qPCR results showed that the EGFR inhibitor Dacomitinib attenuated the suppressive effect of AGO on IFN-related gene expression in ISD/cGAMP-stimulated macrophages...Behavioral tests, including the tail suspension test (TST), forced swim test (FST), and open field test (OFT), demonstrated that AGO significantly ameliorated depression-like behaviors in lupus model mice. Conclusions This study elucidates the molecular mechanism by which the antidepressant AGO modulates STING activity and the subsequent production of IFN-I, thereby laying a theoretical foundation of novel therapeutics for SLE."

Cardiovascular • CNS Disorders • Depression • Herpes Simplex • Immunology • Inflammatory Arthritis • Lupus • Mood Disorders • Sleep Disorder • Systemic Lupus Erythematosus • CCL2 • CXCL1 • CXCL10 • CXCL12 • CXCL5 • CXCL9 • IFNB1 • IRF7 • MX1 • STING

Combined inhibition of DOT1L and BCL-2 induces synergistic anti-leukemic effects in MLL-rearranged acute myeloid leukemia via suppression of the PI3K/AKT pathway. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "This study evaluated the synergistic efficacy of combining the DOT1L inhibitor EPZ004777 with the BCL-2 inhibitor ABT-737. In vivo, combination therapy prolonged survival, restored bone marrow function, and alleviated organ infiltration. These findings demonstrate that dual targeting of DOT1L and BCL-2 exerts synergistic anti-leukemic activity via PI3K/AKT suppression in MLL-rearranged AML, providing a pharmacological rationale for this innovative combination strategy."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • AKT1 • BCL2 • DOT1L • HOXA10 • MLLT10

Time-Resolved Transcriptomic Profiling of Surgical Wounds Identifies Stage-Specific Therapeutic Targets for Residual Ovarian Cancer. (PubMed, Pharmaceutics) - "At T1, WsDEGs were enriched in inflammatory signaling, coagulation, angiogenesis, and immune cell migration, with Vorinostat and Homoharringtonine identified as top candidates to counteract these signatures. At T2, pathways related to cell survival, adhesion, and morphogenesis predominated, with LY-2090314, Artesunate, and Birinapant emerging as potential modulators. At T3, cell-cycle regulation and lipid metabolic pathways were dominant, and Fulvestrant, Atorvastatin, Imatinib, and ABT-737 were predicted to inhibit these processes. Perioperative surgical wounding induces dynamic, stage-specific transcriptomic programs that may promote ovarian cancer progression and alter drug responsiveness. These findings support time-adapted perioperative pharmacologic strategies to optimize postoperative cancer therapy."

Journal • Anesthesia • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

Isatin analogs potentiate the cytotoxicity of venetoclax in acute myeloid leukemia cells (AACR 2024) - "ISA also showed significant synergetic cytotoxicity in combination with ABT-737, a BH3 mimetic inhibitor of Bcl-xL, Bcl-2, and Bcl-w. Furthermore, our aim will be to demonstrate activity in primary patient cells along with preclinical efficacy in AML animal models. To summarize, in vitro findings showed synergetic cooperation between ISA and VEN in combination for effective induction of apoptosis and anti-leukemic activity in AML cells that are sensitive and resistant to VEN."

IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Leukemia • Lymphoma • Oncology • ANXA5 • BCL2L1 • BCL2L2

Global DNA methylation level is associated with the sensitivity of cytotoxic and senotherapeutic drugs in gastrointestinal tumors (AACR 2024) - "The sensitivity of anti-tumor drugs, including the cytotoxic (oxaliplatin and fluorouracil) and five senotherapeutic agents (Dasatinib, Nutlin-3a, Navitoclax, Rapamycin, ABT737), were inferred with Oncopredict R package based on the gene expression profile. DNA methylation of repetitive elements could serve as a biomarker for cytotoxic and senotherapeutic drugs in GC. In addition, our findings suggested the promising value of ALU and LINE-1 methylation-guided chemotherapy with senotherapeutics in GC."

Clinical • Epigenetic controller • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Chemotherapy induced senescence drives peripheral neuropathy (AACR 2024) - "Paclitaxel (PTX), a common treatment for breast cancer, induces CIPN in 61-92% of patients depending on the administered dose...In an independent approach, we found that senolytic drugs (kill senescent cells), such as dasatinib and quercetin (DQ) or ABT737 (ABT), effectively prevented and reversed CIPN in mice...To address the mechanism behind CIPN we have carried out single cell RNA sequencing (scRNA-seq) to identify the cell population senescing in response to chemotherapy. These analyses will allow us to understand the mechanisms that drive CIPN and may lead to new treatments for patients suffering from CIPN."

Breast Cancer • Oncology • Solid Tumor • CDKN2A

UPR/ATF4/Noxa pathway overactivation through SERCA2 inhibition or ONC201 treatment combined with ABT-737 triggers apoptosis in chemoresistant ovarian cancer cells and patient-derived tumor organoids. (PubMed, Cell Death Dis) - "Ovarian cancer has a poor clinical prognosis due to chemoresistance following carboplatin/paclitaxel treatment...The therapeutic efficacy of these combinations was also proved in patient-derived tumor organoid models (PDTO), leading to their structural disintegration and reduced viability. Collectively, our study highlights that ABT-737, through BCL-xL inhibition and synergy with ER stress inducers, triggers ovarian cancer death, offering promising strategies for overcoming chemoresistance in relapsed ovarian cancer."

IO biomarker • Journal • Oncology • Ovarian Cancer • Solid Tumor • ATF4 • BCL2 • BCL2L1

Retinal organoid screening reveals ABT-737 and luminespib as potential agents against a cone- precursor-derived subtype of retinoblastoma. (PubMed, Mol Ther Oncol) - "However, validation in additional retinoblastoma subtypes beyond cone-precursor-derived tumors is essential to determine broader therapeutic applicability and efficacy. Future studies should prioritize testing these agents across diverse Rb genomic and phenotypic subtypes to address potential heterogeneity in treatment response."

Journal • Eye Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • ANXA5 • CASP3 • RB1

Ursolic Acid Attenuates Bone Loss by Stabilizing Osteoblast Mitochondrial Integrity and Inhibiting Downstream Apoptosis via PI3K-AKT-Bcl2 Signaling. (PubMed, Eur J Pharmacol) - "UA promotes osteoblast differentiation and mitigates mitochondrial dysfunction by activating PI3K-AKT-Bcl2 signaling. The findings provide evidence supporting UA as a potential therapeutic candidate for OP."

IO biomarker • Journal • Metabolic Disorders • Osteoporosis • Rheumatology • BCL2

ABT-737 efficiently inhibits hepatocellular carcinoma cell activity via regulating PANoptosis. (PubMed, Discov Oncol) - "ABT-737 exerts potent antitumor effects through the induction of PANoptosis in hepatocellular carcinoma, providing a promising therapeutic strategy for HCC treatment."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • ANXA5 • BAX • BCL2 • CASP3 • NLRP3 • RIPK1

Combination of EGCG and BH3 Mimetic Inhibitor Enhances Apoptosis of MCF-7 and MDA-MB-231 Cancer Cells. (PubMed, Adv Biomed Res) - "EGCG has been shown to possess antitumor properties in breast cancer cells. Moreover, EGCG has the potential to enhance the apoptotic effects of ABT-737 by suppressing the expression of Mcl-1."

Journal • Breast Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • CASP3 • MMP2

Targeted Sensitization of Leukemic T-cells to Anticancer Drugs by SIRT1 Agonist SRT-1720. (PubMed, Anticancer Res) - "SRT-1720 induces oxidative stress and apoptosis in leukemic lymphocytes through SIRT1-independent pathway(s). In contrast, it enhances antioxidant defense in normal lymphocytes through a SIRT1-dependent pathway. These findings highlight the potential of SRT-1720 as an adjuvant to chemotherapy in T-ALL, particularly in drug combinations demonstrating strong synergism, which may allow dose reduction and decreased toxicity."

Journal • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • SIRT1

Senotherapeutic Potential of Araliadiol in Senescent Human Dermal Fibroblasts: An In Vitro Study Using Three Senescence Models. (PubMed, Pharmaceutics) - "Given the cost and reproducibility limitations of existing senescence models, this study established three dermal fibroblast senescence models induced by etoposide, hydrogen peroxide, and ultraviolet A, representing intrinsic and extrinsic aging...The senolytic agent ABT-737 selectively induced apoptosis in senescent fibroblasts but not in non-senescent fibroblasts, validating the models. Araliadiol showed no senolytic activity but demonstrated potential senomorphic effects, including reduced expression of senescence-associated secretory phenotype (SASP) genes (IL1β, IL6, IL8, CCL2, and CXCL1) and NF-κB p65 phosphorylation, suppression of MMP-1 (up to 2.35-fold reduction) and MMP-3 (up to 30.53-fold reduction) expression and AP-1 activation, and increased extracellular procollagen type I content (up to 18.35% increase). Araliadiol exerted senomorphic-but not senolytic-effects across three validated dermal fibroblast senescence models, supporting its potential as a..."

Journal • Preclinical • CCL2 • CDKN1A • CXCL1 • CXCL8 • IL1B • IL6 • MMP1 • MMP3

Curcumin Enhanced the Chemosensitivity of Breast Cancer Cells through the Intrinsic Pathway of Apoptosis. (PubMed, Asian Pac J Cancer Prev) - "In conclusion, curcumin demonstrates anti-tumor activity in human breast cancer cells by inhibiting colony formation, cell migration, and cell survival. Furthermore, curcumin can augment the apoptotic effect of ABT-737 by suppressing the expression of Mcl-1."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • CASP3 • MMP2

Viral mimicry in AML is linked to immune activation but not BCL2 inhibitor sensitivity (ASH 2025) - "Drug sensitivity was assessed using ex-vivo area under the curve (AUC) values for azacytidine, venetoclax, and ABT-737. Although the clinical impact is not yet clear, these findings highlight a unique immune-related signature that could help guide future studies of immunotherapy or hypomethylating agents in AML. Further clinical validation is needed."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Solid Tumor • CD8 • HAVCR2 • MX1 • PD-1 • PD-L1 • RSAD2 • TIGIT

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