tanespimycin (BMS-722782) / BMS - LARVOL DELTA

Bio-Inspired Albumin Platform for Synergistic Co-Delivery of Tanespimycin, Dasatinib, and Quercetin and Enhanced Therapeutic Efficacy in Triple-Negative Breast Cancer. (PubMed, Adv Healthc Mater) - "(T-D-Q)-BSA Cs also inhibited TNBC-based tumor growth in two zebrafish xenograft in vivo models. In conclusion, the efficacy of (T-D-Q)-BSA Cs as a novel therapeutic strategy to eradicate TNBC in vitro and in vivo was demonstrated."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • IL6

Trastuzumab-TKI combination in HER2-Positive tumors: a FAERS-Based safety profile and multimodal analysis of Tanespimycin's role in enhancing targeting of the HSP90AA1-PI3K-Akt-mTOR axis. (PubMed, Front Pharmacol) - "This study addresses the safety profiles and molecular mechanisms of trastuzumab monotherapy and its combination with lapatinib, neratinib, and tucatinib for treating HER2-positive tumors. This study establishes a novel framework for drug safety evaluation and provides a theoretical rationale for optimizing therapeutic strategies in HER2-positive tumors. These findings highlight the potential advantages of combination therapies regarding AE latency and elucidate the critical role of HSP90AA1."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDC37 • HER-2 • HSP90AA1

Analysis of motor-based transport in primary cilia by dynamic mode decomposition of live-cell imaging data. (PubMed, J Cell Sci) - "However, when retrograde dynein-2 function is inhibited by Ciliobrevin D or Tanespimycin, both anterograde and retrograde IFT velocities decrease in parental cells, as expected, but remain unchanged in KIF13B mutant cells. Structured illumination, confocal, and STED microscopy further show that KIF13B localizes to the ciliary membrane and concentrates at the periciliary membrane region and the centriolar subdistal appendages, below the distal appendage marker FBF1. Our improved kymograph approach provides new insight into KIF13B ciliary function and simplifies the quantitative analysis of ciliary protein transport."

Journal

Heat Shock Protein Inhibitor Tanespimycin (17AAG) Suppresses SARS-CoV-2 Main Protease Activity and Is More Potent Than Clinically Approved Antiviral Nirmatrelvir. (PubMed, Chembiochem) - "We further showed that 17AAG retains its covalent binding and structure-disrupting activity against the nirmatrelvir-resistance M165I variant. Additionally, since HSP90 is important for viral protein stability, virion assembly, and modulation of host immune response, 17AAG is a promising, versatile drug candidate that could accelerate antiviral development for COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CDC37

Hsa_circ_0000520 Promotes Invasion and Metastasis of Breast Cancer Cells by Targeting HSP90AA1. (PubMed, Breast Cancer (Dove Med Press)) - "Rescue experiments were conducted using the HSP90AA1 inhibitor tanespimycin...Importantly, its elevated expression correlates with advanced clinical stage, specific molecular subtypes, and poor prognosis in BC patients. Our research results revealed an unrecognized regulatory axis, in which hsa_circ_0000520 facilitates BC cells progression by coordinating with HSP90AA1, highlighting hsa_circ_0000520 could be a promising diagnostic indicator and potential treatment target for BC."

Journal • Breast Cancer • Oncology • Solid Tumor • CDC37 • HSP90AA1

CCNJL as a Prognostic Biomarker and Therapeutic Target in Cholangiocarcinoma. (PubMed, Curr Med Chem) - "CCNJL has the potential to act as a valuable prognostic indicator and immunotherapy target in CHOL. Its expression pattern and associations with clinical outcomes, immune characteristics, and drug sensitivity highlight its potential for improving diagnostic and therapeutic approaches. Future research should focus on elucidating the underlying mechanisms and validating these findings in larger cohorts."

Biomarker • IO biomarker • Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • CD8

Heat shock protein inhibitors suppress cytokine-induced DUOX2 mRNA and protein expression in human pancreatic cancer cells in a JAK, STAT dependent manner (AACR 2026) - "Using a panel of human pancreatic cancer cell lines (BxPC-3, AsPC-1 and CFPAC-1), we found that two different Hsp90 inhibitors, Tanespimycin (17-AAG) and Ganetespib (STA-9090), inhibit JAK1 and JAK2 kinases, blocking cytokine-induced, JAK-regulated STAT phosphorylation...Furthermore, the JAK1/2 inhibitor Ruxolitinib inhibits IL-4 induced and JAK-mediated STAT6 phosphorylation, and DUOX2 mRNA and protein expression in BxPC-3 cells...Either remaining Hsp90 protein or other isoforms of Hsp90 in cells may compensate decreased Hsp90 function after siRNA knockdown. Our data suggests that Hsp90 inhibitors, through blocking the cytokine-activated JAK-STATs oncogenic signaling pathway and their downstream genes such as DUOX2, VEGF-A, MMP-7 and PD-L1expression, may be a valuable therapeutic approach for inflammation-associated pancreatic cancer."

IO biomarker • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CDC37 • DUOX2 • HIF1A • IFNA1 • IL17A • IL4 • MMP7 • PD-L1 • STAT1 • STAT3 • STAT6

The cardiovascular-immune axis: crosstalk and therapy in atherosclerosis, myocarditis and vasculitis. (PubMed, Front Immunol) - "Furthermore, precision strategies targeting these hubs are evaluated, utilizing agents such as Plerixafor, Lycorine, Dexamethasone, and Tanespimycin. Finally, emerging frontiers, including natural products and biomaterials, are assessed, providing a perspective on current clinical trials and future directions for resolving cardiovascular inflammation."

Journal • Review • Atherosclerosis • Cardiovascular • Immunology • Inflammation • Vasculitis • CXCR4 • HSPA1A • PYCARD • TSC22D3

Heat shock protein inhibitors suppress cytokine-induced DUOX2 mRNA and protein expression in human pancreatic cancer cells in a JAK-STAT dependent manner [WITHDRAWN] (AACR 2025) - "Using a panel of human pancreatic cancer cell lines (BxPC-3, AsPC-1 and CFPAC-1), we found that two different Hsp90 inhibitors, Tanespimycin (17-AAG) and Ganetespib (STA-9090), inhibit JAK1 and JAK2 kinases, blocking cytokine-induced, JAK-regulated STAT phosphorylation...Furthermore, the JAK1/2 inhibitor Ruxolitinib inhibits IL-4 induced and JAK-mediated STAT6 phosphorylation, and DUOX2 mRNA and protein expression in BxPC-3 cells...Either remaining Hsp90 protein or other isoforms of Hsp90 in cells may compensate decreased Hsp90 function after siRNA knockdown. Our data suggests that Hsp90 inhibitors, through blocking the cytokine-activated JAK-STATs oncogenic signaling pathway and their downstream genes such as DUOX2, VEGF-A, MMP-7 and PD-L1expression, may be a valuable therapeutic approach for inflammation-associated pancreatic cancer."

IO biomarker • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CDC37 • DUOX2 • HIF1A • IFNA1 • IL17A • IL4 • MMP7 • PD-L1 • STAT1 • STAT3 • STAT6

Drug-centric prior improves drug response signature identification in partially overlapping, large-scale pharmacogenomic datasets (AACR 2024) - "We evaluate our performance in three ways: 1) we test if the joint model improves the prioritization of known consensus biomarkers for the drugs shared between the two cohorts; 2) we test if the joint model improves the recapitulation of shared drug mechanism of action as compared to the single dataset models; 3) we evaluate the joint models with respect to pathway enrichment as compared to the single dataset models. We evaluated the performance of our joint model for 5 drugs shared between the 2 resources: selumetinib, tanespimycin, nutlin 3A, mirdametinib and PLX4720. We present an application of a Bayesian group factor analysis model, where we employ a drug-centric prior to transfer information about drugs screened in multiple datasets. We show that joint models leveraging partially overlapping large-scale pharmacogenomic datasets from the Broad and Sanger institutes can overall improve drug signature identification."

Biomarker • Genomic data • Oncology

Integrating Network Toxicology, Machine Learning, and Experimental Evidence Reveals Candidate Targets and Pathways in PCDD/F-Related Colon Cancer. (PubMed, Food Chem Toxicol) - "Consistent with these in silico findings, exposure of mice to 24 μg/kg TCDF significantly increased the expression of Mmp7 and Hsp90aa1 in murine colonic tissues, increased the levels of proinflammatory cytokines Ifn-γ, Il-1β, and Il-6, and downregulated the expression of Mucin 2 (MUC2). Connectivity Map analysis based on the PCDD/F-related gene signature identified five candidate compounds targeting MMP7 and HSP90AA1, of which four HSP90 inhibitors (tanespimycin, alvespimycin, NVP-AUY922 and AT-13387) showed negative connectivity scores, suggesting potential to reverse the pollutant-induced expression profile."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CDC37 • IFNG • IL1B • IL6 • MMP7 • MUC2

A High-Density Microchamber Array for the Analysis of Extracellular Vesicles Derived from Single Cells under Drug Treatment. (PubMed, Anal Chem) - "Here, we study EV secretion from individual breast cancer cells and the changes under treatment with the HSP90-inhibiting cancer drug tanespimycin (17AAG)...Moreover, our results emphasize that using CD63 as the sole EV capture protein may hide important EV subpopulations. Overall, our platform may support future choices of EV biomarkers for diagnostic and biomedical purposes and help in understanding the heterogeneous drug response of cancer cells."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD63 • CD81 • CD9 • CDC37 • HER-2 • HSP90AA1

A small-molecule HSP90 inhibitor, NVP-HSP990, alleviates rotavirus infection. (PubMed, J Virol) - "In this study, we demonstrated that NVP-HSP990, a novel small-molecule heat shock protein 90 (HSP90) inhibitor, inhibited RV infection with a fascinatingly higher selectivity index compared to conventional HSP90 inhibitors like geldanamycin and its derivative tanespimycin (17-allylamino-17-demethoxygeldanamycin [17-AAG])...As a result, NVP-HSP990 significantly alleviated the severity of RV-induced diarrhea. Given its excellent oral efficacy and systemic penetration previously reported, NVP-HSP990 emerges as a promising HSP90-targeted candidate capable of addressing both intestinal and possible extraintestinal RV infections, which also repositions HSP90 inhibition as a viable strategy in RV management."

Journal • Infectious Disease • Inflammation • Rotavirus Infections • CDC37 • IL17A

Andrographolide Promotes Ferroptosis in Pancreatic Cancer via Targeting and Activating HSP90/GPX4 Ubiquitination. (PubMed, Biofactors) - "ADG suppresses HSP90 expression, and tanespimycin prevents ADG-induced cytotoxicity, showing that HSP90 is ADG's main target in activating intracellular activities...The findings strongly suggest that ADG may treat PC. ADG's pharmacokinetics and other effects must be studied in patients' clinical trials to make it a pancreatic cancer therapy option."

IO biomarker • Journal • Metabolic Disorders • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Targeted Protein Degradation • CDC37 • GPX4 • HSP90AA1

Identification of key genes in pancreatic ductal adenocarcinoma with biologically informed deep neural network. (PubMed, J Gastrointest Oncol) - "Through molecular docking analysis, we found that ursolic acid (UA) and tanespimycin might target JAG1, MET, and PLAU...Our study demonstrated that JAG1, MET, and PLAU were significantly overexpressed and associated with poor outcomes in PDAC patients. More importantly, these genes are involved in the crosstalk between tumour and immune cells, which indicates that these genes may serve as novel targets for combination immunotherapy in the treatment of PDAC."

IO biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • JAG1 • PLAU

Targeting treatment-resistant Systemic Lupus Erythematosus through transcriptome-informed drug repurposing (ACR Convergence 2025) - "To guide precision repurposing, we applied a transcriptome-driven strategy to identify compounds that either mimic the molecular effects of standard therapies or reverse gene expression profiles associated with treatment resistance. Paired whole-blood transcriptomes from 31 SLE patients treated with rituximab (n=8), belimumab (n=13), or cyclophosphamide (n=10) were analyzed to define drug-specific signatures (absolute log₂FC > 0.58, p < 0.05)...Rituximab's signature aligned with mTOR blockers (everolimus, dactolisib), PI3K inhibitors (PIK-75, ZSTK474), JAK2 inhibitors (fedratinib) and agents downregulating the p38-MAPK pathway (OXA)... Our analysis delineates molecular correlates of therapeutic response and identifies candidate drugs capable of emulating molecular effects of standard SLE therapies or reversing gene expression patterns associated with treatment failure, offering a framework for drug repurposing in difficult-to-treat SLE."

IO biomarker • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • BCL2 • CDC37

Combination of B-AP15 and HSP90 inhibitor tanespimycin induces ROS-mediated cytotoxicity in human lung cancer cells. (PubMed, BMC Pharmacol Toxicol) - No abstract available

Journal • Lung Cancer • Oncology • Solid Tumor • CDC37

Identification of biomarkers and therapeutic targets of schizophrenia using glutamine metabolism. (PubMed, Asian J Psychiatr) - "This study demonstrates the potential causal association of GM-related genes in SCZ, developed a precise diagnostic model, and proposed novel targeted therapeutic strategies."

Biomarker • Journal • CNS Disorders • Developmental Disorders • Psychiatry • Schizophrenia • SLC1A5

Ginger-derived vesicle-like nanoparticles loaded with curcumin to alleviate ionizing radiation-induced intestinal damage via gut microbiota regulation. (PubMed, Gut Microbes) - "This beneficial effect was attributed to the identified radioprotective metabolites secreted by A. muciniphila, such as tanespimycin (17-AAG), which was demonstrated to deactivate AKT/NF-κB signaling pathway. These findings reveal the impact of plant products on radioprotective microbes and metabolites to target host processes and alleviate IR-induced intestinal damage, shedding light on new insights in the development of novel radioprotectants."

Journal • Gastrointestinal Disorder

Tick-Tock: Cancer Cell Division Cycle Clocks Strike Midnight. (PubMed, Int J Mol Sci) - "To induce these potential forced overgrowth effects, we suggest targeting the cell division cycle regulatory enzyme, the anaphase-promoting complex/cyclosome (APC/C), to suppress-but not inhibit-its activity. We conclude by proposing experiments to test this hypothesis in which an APC/C inhibitor, such as a low level of proTAME, is combined with the clinically approved heat-shock protein 90 (HSP90)-inhibitor pimitespib (TAS-116) or the pre-clinical molecule tanespimycin, which, to the best of our knowledge, are combinations that have not been investigated before."

Journal • Review • Oncology • CDC37 • HSP90AA1

Pd, S co-modified Prussian blue analogues nanocomposites for MRI guided combined mitochondria-targeting cancer therapy with tumor microenvironment remodeling, multienzyme-like catalysis and mild photothermal therapeutic effect. (PubMed, Colloids Surf B Biointerfaces) - "To construct efficient nanoplatform for prostate cancer therapy, a HSP 90 protein inhibitor, tanespimycin was loaded on Pd-S-CNMF (17Pd-S-CNMF) to inhibit the level of HSP 90 protein, thus increasing the outcome of subsequent photothermal therapy...Benefiting from these amazing properties, the as-prepared 17Pd-S-CNMF could effectively inhibit the growth of prostate cancer in vitro and vivo. Our findings provide a paradigm for construction of efficient nanocomposites as nanoplatform for cancer diagnose and treatment."

Biomarker • Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HSP90AA1

High throughput drug screening on head and neck cancer organoids reveals novel therapeutic strategies (COSM 2025) - "Of these, 4 exhibited ≥ 50% selectivity for tumor tissue compared to normal (pracinostat, tanespimycin, SB-743921, and mocetinostat). High-throughput drug screening across eight normal, dysplastic, and HNSCC PDOs revealed protein and epigenetic targeting drugs to have the most proportional hits. Specifically, HSP90 and HDAC inhibitors were most effective within their drug class. Pending dose response experiments and validation across a larger cohort, these results provide potential novel protein and epigenetic targeting strategies as promising approaches in HNSCC."

Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDC37 • HSP90AA1

High throughput drug screening on head and neck cancer organoids reveals novel therapeutic strategies (AHNS-COSM 2025) - "Of these, 4 exhibited ≥ 50% selectivity for tumor tissue compared to normal (pracinostat, tanespimycin, SB-743921, and mocetinostat). High-throughput drug screening across eight normal, dysplastic, and HNSCC PDOs revealed protein and epigenetic targeting drugs to have the most proportional hits. Specifically, HSP90 and HDAC inhibitors were most effective within their drug class. Pending dose response experiments and validation across a larger cohort, these results provide potential novel protein and epigenetic targeting strategies as promising approaches in HNSCC."

Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDC37 • HSP90AA1

Pharmacological landscape of endoplasmic reticulum stress: uncovering therapeutic avenues for metabolic diseases. (PubMed, Eur J Pharmacol) - "It examines small molecules such as tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid (4-PBA), repurposed drugs like 17-AAG (17-N-allylamino-17demethoxygeldanamycin (tanespimycin)) and berberine, and phytochemicals such as resveratrol and hesperidin. The review emphasizes challenges in translating these therapies to clinical applications, such as toxicity, off-target effects, limited bioavailability, and the lack of large-scale randomized controlled trials (RCTs). It also highlights the potential of personalized medicine approaches and pharmacogenomics in optimizing ER stress-targeting therapies."

Journal • Review • Alzheimer's Disease • CNS Disorders • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Movement Disorders • Parkinson's Disease

Consensus nonnegative matrix factorization reveals metastatic gene expression program and identifies E74-like ETS transcription factor 3 confers to the lymph nodes metastasis in papillary thyroid cancer. (PubMed, Endocrine) - "This study highlights the critical role of GEP and ELF3 in driving PTC progression and metastasis. Drug screening revealed that tanespimycin and vemurafenib were effective in targeting GEP3high cells, offering therapeutic potential for aggressive PTC. These insights advance precision strategies for managing metastatic and heterogeneous PTC by targeting ELF3-driven pathways."

Journal • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • BRAF • ELF3 • TCF3