luminespib (AUY922) / Ligand - LARVOL DELTA

Ten Non-N-Terminal-Domain Inhibitors of the Hsp90 Chaperone Machine Fail to Elicit Canonical Proteome-wide Responses in Jurkat Leukemia Cells. (PubMed, J Proteome Res) - "By comparing these changes to those induced by the N-terminal Hsp90 inhibitor NVP-AUY922, we find that none of our 10 AHI compounds induce the canonical changes characteristic of N-terminal Hsp90 inhibition...We conclude that none of these 10 AHI compounds induce apoptosis in Jurkat cells via Hsp90 inhibition. Because these compounds have been previously advanced as Hsp90 inhibitors, results here indicate that insular client depletion assays are inadequate to the task of validating Hsp90 inhibition in living cells."

Journal • Hematological Malignancies • Leukemia • Oncology • CDC37 • HSP90AA1

Integrative drug repositioning identifies FDA-approved inhibitors of HSP90AA1 with therapeutic potential in colorectal cancer. (PubMed, Bioorg Chem) - "Docking and 200 ns molecular dynamics showed stable binding of all four in the HSP90α ATP-binding pocket, with hydrogen bonding and favorable MM/GBSA free energies (-30.59 kcal/mol for danazol to -37.37 kcal/mol for rifapentine; reference NVP-AUY922 -47.99 kcal/mol). In vitro, the drugs suppressed proliferation and induced apoptosis in HCT116, LoVo, and HCT-15 cells, with IC₅₀ values of 2.60-13.15 μM. These results identify unreported HSP90AA1 inhibitors in CRC and establish a generalizable repositioning framework."

FDA event • Journal • Colorectal Cancer • Oncology • Solid Tumor • CDC37 • HSP90AA1

A multimodal analysis suggests partial IRF8/TLR7-associated myeloid transcriptional convergence between diabetic kidney disease and Parkinson's disease. (PubMed, PLoS One) - "DKD and PD show limited genome-wide overlap but partial convergence of myeloid- and microglia-enriched inflammatory signals associated with IRF8 and TLR7. These findings provide testable hypotheses rather than evidence of a conserved causal pathway or validated cross-disease treatment."

Journal • CNS Disorders • Diabetic Nephropathy • Movement Disorders • Nephrology • Parkinson's Disease • Renal Disease • IRF8 • TGFB1 • TLR7

Bioinformatics-based identification of ferroptosis-related biomarkers and immune infiltration in retinoblastoma. (PubMed, Transl Cancer Res) - "Drug sensitivity analysis suggested AUY922, AG.014699, and AMG.706 as candidate therapeutic agents. This study identified three ferroptosis-related genes (FRGs) as potential diagnostic biomarkers of RB. Their association with immune cell infiltration provides new insights into the molecular mechanisms of RB and highlights potential therapeutic opportunities."

Biomarker • Journal • Eye Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • HSPB1 • NFE2L2

Plasmodium falciparum HSP90 inhibitors show divergent resistance despite a shared ATP-binding site. (PubMed, Cell Rep) - "We propose AUY-922's lower resistance risk reflects engagement of multiple HSP90 family members. These findings demonstrate that resistance risk cannot be predicted from binding site identity alone, informing development of more durable therapeutics."

Journal • Infectious Disease • Malaria • CDC37

Luminespib and AZ5104 are effective antithrombotic drugs via targeting the platelet Ero1α-PDI pathway. (PubMed, Sci Adv) - "Both compounds potently reduced arterial thrombosis in mice without prolonging bleeding time. Our work establishes Luminespib and AZ5104 as clinical-stage antithrombotic agents that target the platelet Ero1α-PDI system, offering an effective strategy to achieve potent antithrombosis without compromising hemostasis."

Journal • Cardiovascular • Hematological Disorders • ERO1A

Combination therapy with HSP90 inhibitors and NanoPulse stimulation synergistically impedes hepatocellular carcinoma and breast cancer growth in mice. (PubMed, Sci Rep) - "Here we present results of a combination therapy employing two HSP90 inhibitors (AUY-922 or 17-AAG) and NPS to ablate cancer growth...Furthermore, HI and NPS, when combined, were used in lower doses than those required to achieve similar results, thus reducing the risk of potential side effects. By acting synergistically, combination therapy with HSP90 Inhibitors and NanoPulse Stimulation acts through distinct mechanisms, demonstrating a potent treatment that results in synergistic tumor mass reduction."

Journal • Preclinical • Breast Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CASP3 • CDC37

A novel mitochondrial-related signature to decode tumor immunity and predict survival in chromophobe renal cell carcinoma. (PubMed, Immunobiology) - "Notably, our computational analysis based on GDSC's pRRophetic algorithm suggests that LCL161 and UMI-77 may be more effective in the low-risk group, while sapitinib and luminespib show potential efficacy in the high-risk group. In conclusion, our study indicates this model holds high promise as a reliable biomarker for outcome prediction and precision-medicine stratification in chRCC patients."

Journal • Tumor mutational burden • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • RECQL4 • TERF1

Nanotechnology-based reformulation of AUY922 mitigates retinal toxicity and retains potent anti-tumor activity. (PubMed, Nanomedicine) - "These findings support that nanoparticle reformulation can decouple antitumor efficacy from tissue-specific toxicity. FLIM02 suggests potential to reduce ocular toxicity while preserving antitumor activity, meriting further mechanistic studies and longitudinal preclinical models."

Journal • Nephrology • Oncology • GFAP

A computational framework identifies a matrisome-related gene signature for bladder cancer prognosis and prioritizes candidate compounds. (PubMed, Comput Biol Chem) - "This study highlights the prognostic relevance of MRGs in BLCA. The nine-gene signature may serve as a useful framework for risk stratification in BLCA, while the identified risk genes and candidate compounds provide a basis for further biological and experimental investigation rather than direct therapeutic inference."

Gene Signature • Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD3D • CLDN5 • RBP7 • SERPINE2 • TSPAN8

YAP-TEAD-mediated tumor suppression and immune modulation of gastric adenocarcinoma by HSP90 inhibition (AACR 2025) - "Our findings highlighted the suggestion of targeting HSP90 in GAC therapy via down-regulating YAP1/TEAD signaling. Further, results suggest that AUY922's ability to reshape the GAC TME favoring the host sets the stage for a clinical trial that combines HSP90 and checkpoint inhibition, where HSP90 could serve as a biomarker for patient selection."

IO biomarker • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • CDC37 • HSP90AA1 • YAP1

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

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

Drug-tolerant pannen cells as precursors of acquired resistance: Opportunities for early intervention against relapse (ENETS 2026) - "mqSCI resolved the longitudinal stress adaptation (0-21 days) to six clinical and ex - perimental anticancer drugs (Temozolomide, Everolimus, Suni - tinib, 5-FU, SCH772984, AUY922) with different mechanisms of action... Our study confirms the presence of DTCs in Pan - NEN according to consensus hallmarks and demonstrates the utility of mqSCI for measuring adaptive reprogramming over time and for developing DTC-specific co-treatment strategies."

Preclinical • Immunology • Metabolic Disorders

Diversity of Gut Microbiota and Metabolites in Benign Prostatic Hyperplasia with Different Prostate Volumes. (PubMed, Eur Urol Open Sci) - "Akkermansia (ASV549) may affect prostate volume through the regulation of intestinal amino acid metabolism and may negatively affect prostate-specific antigen levels by inhibiting heat shock protein (HSP) 90 (luminespib)...In this study, we identified the potential associations between gut and both prostate volume and benign prostatic hyperplasia symptoms. These findings suggest that dietary interventions or fecal microbiota transplantation may represent potential strategies for modulating prostate health in the future."

Journal • Benign Prostatic Hyperplasia • Transplantation

Harnessing Ubiquitin-Proteasome System-Related Genes to Identify Subtypes of Bladder Cancer and Reveal Immune Landscape. (PubMed, Am J Mens Health) - "Somatic mutations demonstrated that the mutation rate of Cluster B was higher than that of Cluster A. In addition, candidate drugs for two clusters of patients were predicted, with Lapatinib, Doramapimod, and SCH772984 may be potential drugs for Cluster A patients. Luminespib, Staurosporine, and Dasatinib may be more suitable for Cluster B patients. The study provides a reference for guiding the clinical treatment of BLCA patients."

IO biomarker • Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • BTLA

Synergistic Inhibition of PI3K and HSP90 Enhanced Antitumorigenic Efficacy in Adrenocortical Carcinoma. (PubMed, Res Sq) - "Quantitative high-throughput drug combination screening identified potent synergy between phosphatidylinositol-3-kinase (PI3K) inhibitor, PIK75 and heat shock protein 90 (HSP90) inhibitors, Ganetespib (STA9090), HSP990, or Luminespib (NVP-AUY922). Further antitumor efficacy was confirmed by the BGT226-STA9090 combination in human ACC xenograft model and five PDOs with different pathogenic mutations. Conclusively, the combinations of PI3K and HSP90 inhibitors were highly effective in preclinical studies, warranting a clinical trial in patients with advanced ACC."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CDC37 • HSP90AA1

Shared Binding Site but Divergent Resistance Profiles Uncover Novel Resistance Mechanisms in Plasmodium HSP90 Inhibitors. (PubMed, bioRxiv) - "Based on these data, we propose a multi-target hypothesis where AUY-922's lower resistance risk stems from engaging multiple HSP90 family members. Our findings reveal how enhanced drug-target binding can paradoxically correlate with resistance and demonstrate that resistance risk cannot be predicted from binding site identity alone, providing insights for developing more durable drugs across therapeutic areas."

Journal • Infectious Disease • Malaria • CDC37

Luminespib protects against dexamethasone-induced hepatic, vascular, and metabolic abnormalities in rats. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "According to our results, such outstanding improvements were attributed to (i) restoring cellular oxidant balance (GSH, MDA & NO), (ii) curbing NF-κB/TNF-α/MCP-1 inflammatory cascade, (iii) HSP90 inhibition with reduced expression of glucocorticoid receptors (GR), (iv) reduced expression of the endoplasmic reticulum stress sensors (CHOP & PERK), (v) activation of protein degradation pathways that degrade the misfolded GR including proteasomal degradation (20 S proteasome) and autophagy (BECLIN1). In conclusion, the findings in this study provide valuable insights into the therapeutic potential of LUM in protecting against DEX-induced deleterious effects on hepatic and aortic tissue in order to get the optimum therapeutic outcome from DEX."

Journal • Preclinical • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Targeted Protein Degradation • BECN1 • CDC37 • NR3C1 • TNFA

Self-Assembled Dictamni Cortex Nanoparticles Ameliorate Psoriasis by Epigenetic Modulation of HSP90AB1 and Suppression of the Inflammatory Response. (PubMed, Adv Sci (Weinh)) - "NB significantly suppresses keratinocyte hyperproliferation, inflammation, and oxidative stress in both M5 (a cocktail of cytokines)-treated human epidermal keratinocytes (HEKa) cells and imiquimod (IMQ)-induced psoriatic mice...Notably, NB demonstrated superior therapeutic efficacy over the canonical HSP90 inhibitor AUY922. This study highlights NB as a promising topical nanotherapy for psoriasis, integrating TCM with modern nanotechnology to overcome pharmacological limitations. The underlying molecular mechanisms of NB are elucidated through the CTCF-HSP90AB1-STAT3 axis."

Journal • Dermatology • Immunology • Inflammation • Psoriasis • CDC37 • HSP90AB1

Identification of Ifitm1 as a Pivotal Gene in Mouse Spinal Cord Injury Using Comprehensive Machine Learning Algorithms. (PubMed, Mediators Inflamm) - "Utilizing the CMap database along with molecular docking investigations, the small-molecule drug NVP-AUY922, which interacts with Ifitm1, was discovered. Experimental assessments revealed that Ifitm1 is linked to macrophage inflammation following SCI. This study revealed the importance of granulocyte subsets and Ifitm1 in SCI, proposed Ifitm1 as a potential therapeutic target, and provided new insights into the molecular mechanisms of SCI."

Journal • Preclinical • CNS Disorders • Inflammation • Orthopedics

Exploration of prognostic genes associated with lymphangiogenesis in breast cancer based on transcriptomics and experimental verification. (PubMed, PeerJ) - "Additionally, drugs like AUY922 and AZ628 showed considerable potential in treating BC. RT-qPCR results for these four genes in clinical samples aligned with the bioinformatics findings. This study identified and validated four prognostic genes-ZIC2, CD24, CEBPD, and CCL19-that are associated with BC and may provide novel targets for diagnostic and therapeutic strategies."

Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • BRCA • CCL19 • CD24 • EGFR • ZIC2

Aqueous Extract of Evodia lepta Merr. Attenuates Influenza Virus Infection via Inhibition of the HSP90/NF-κB Axis. (PubMed, J Ethnopharmacol) - "ELM exerts significant therapeutic effects against influenza virus infection in vivo, likely through inhibition of HSP90/NF-κB signaling axis. These findings support the potential of ELM as a novel antiviral agent or adjunct therapy for the treatment of influenza."

Journal • Infectious Disease • Influenza • Respiratory Diseases • CDC37 • HSP90AA1

Preclinical Investigation Of Phosphatidylinositol-3-kinase And Heat Shock Protein 90 Inhibitors Combination Therapy In Adrenocortical Carcinoma (ENDO 2025) - "We determined the effective doses and cytotoxicity of the HSP90 inhibitors (STA9090, HSP990, NVP-AUY922) and PI3K inhibitors (PIK-75, BGT-226) and their combinations in preclinical models of ACC. Further validation of synergistic efficacy of BGT226 and STA9090 in NOD SCID-gamma mice showed a reduction in the mean volume of ACC xenografts in STA9090-BGT226 treatment group to 28.4% of the vehicle control group and 38.4% and 37.7 % of those in STA9090-only and BGT226-only groups, respectively. In conclusion, the synergistic combinations of the PI3K and HSP90 inhibitors were effective in preclinical studies of ACC, warranting a clinical trial in patients with advanced ACC."

Combination therapy • Late-breaking abstract • Preclinical • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • AKT2 • CDC37 • HSP90AB1 • PIK3R1

Preclinical Investigation Of Phosphatidylinositol-3-kinase And Heat Shock Protein 90 Inhibitors Combination Therapy In Adrenocortical Carcinoma (ENDO 2025) - "We determined the effective doses and cytotoxicity of the HSP90 inhibitors (STA9090, HSP990, NVP-AUY922) and PI3K inhibitors (PIK-75, BGT-226) and their combinations in preclinical models of ACC. Further validation of synergistic efficacy of BGT226 and STA9090 in NOD SCID-gamma mice showed a reduction in the mean volume of ACC xenografts in STA9090-BGT226 treatment group to 28.4% of the vehicle control group and 38.4% and 37.7 % of those in STA9090-only and BGT226-only groups, respectively. In conclusion, the synergistic combinations of the PI3K and HSP90 inhibitors were effective in preclinical studies of ACC, warranting a clinical trial in patients with advanced ACC."

Combination therapy • Preclinical • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • AKT2 • CDC37 • HSP90AB1 • PIK3R1