luminespib (AUY922) / Ligand - LARVOL DELTA

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

Dienogest Impact on DIE Lesions and Prognostic Treatment Selection Through Gene Expression and Histological Presentation (WCE 2025) - "The impact of NFKB and HSP90 inhibitors Triptolide and Luminespib on endometrial epithelial cells was validated in high content screening of organoids. Novel compounds for epithelial dominated endometriotic lesions were identified. Together this study provides a genuine pathway to stratify the current approach to endometriosis treatment."

Endometriosis • Fibrosis • Gynecology • Immunology • Women's Health • CDC37 • CXCL1 • CXCL12 • CXCR4 • PGR • SDC4

Unveiling the HSP90 inhibitor mediated effects on endoplasmic reticulum stress and redox signaling:from a cancer inhibitor to retinal degeneration catalyst. (PubMed, Free Radic Biol Med) - "AUY922 can compensate for the high toxicity and instability of traditional inducers in RD modeling. These results not only enrich our understanding of the toxicology of AUY922 but also provide clues for establishing reliable RD models."

Journal • Oncology • Ophthalmology • ATF4 • CDC37

HSP90 and the cancer transcriptome: a comprehensive review of inhibitors and mechanistic insights. (PubMed, Int J Clin Oncol) - "It systematically investigates the effects of HSP90 inhibitors, including AUY922, B11B021, CCT-018159, D7-gedunin, geldanamycin, and gedunin, across a range of cancer cell lines (HCC151, HT29, MCF7, PC3, VCAP, and A375) and a normal HA1E cell line, using data from the CLUE database...The findings suggest that HSP90 inhibitors exhibit varying mechanisms of action across different cancer cell lines despite the presence of some common targets. These insights highlight the need for further investigation into the precise mechanisms of HSP90 inhibitors to optimize their therapeutic potential in different cancers."

Journal • Review • Oncology • CDC37 • HSP90AA1 • HSP90AB1 • IL10 • IL7

Exploring WNT pathway dysregulation in serrated colorectal cancer for improved diagnostic and therapeutic strategies. (PubMed, Front Genet) - "We developed a WNT-derived subtyping method to identify SCC from canonical CRC, which enhances the molecular understanding of this severe cancer subtype and provides potential therapeutic strategies. Our findings suggest that SCC patients may benefit from the HSP90 inhibitor NVP-AUY922, highlighting its potential as a targeted therapy."

Journal • Colorectal Cancer • Oncology • Solid Tumor • BRAF • CD8 • CDC37 • MLH1

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

Construction of a risk model associated with tryptophan metabolism and identification of related molecular subtypes in laryngeal squamous cell carcinoma. (PubMed, Front Genet) - "Besides, the drug sensitivity analysis showed that the low -risk subgroup was notably sensitive to Salubrinal, Lenalidomide, Metformin, while high -risk subgroup was more responsive to Docetaxel, AUY922, Embelin. Eventually, two clusters of LSCC samples had notable correlations with LSCC prognosis. The above results indicated that the risk model consisted of TMRGs (SERPINA1, TMC8, RENBP, SDS and FAM107A) was constructed in LSCC, contributing to studies related to the prognosis and treatment of LSCC."

IO biomarker • Journal • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • SERPINA1

Integrated Analysis of Bulk and Single-Cell RNA Sequencing Data Reveal a Novel Prognostic Signature of Combining Cuproptosis- and Ferroptosis-Related Genes in Hepatocellular Carcinoma. (PubMed, Int J Mol Sci) - "A statistically significant difference in the efficacy of sorafenib was found between the two CFRG score groups...Molecular docking analysis revealed that DLAT and SLC2A1 had a strong binding affinity toward camptothecin, rapamycin, dactolisib, and luminespib. The correlation between the CFRG score and single-cell characteristics was further explored. The study depended on our understanding of the biological function of CFRGs in HCC and provided new insights for developing treatment strategies."

Biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CD4 • DLAT • SLC2A1

The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art. (PubMed, Eur Respir Rev) - "Experimental drugs such as geldanamycin and its derivatives 17-AAG (17-N-allylamino-17-demethoxygeldanamicin) and 17-DMAG (17-dimethylaminoethylamino-17-demethoxigeldanamycin), along with AUY-922, 1G6-D7, AT-13387, TAS-116 and myricetin, have been found to reduce lung fibrosis in both in vivo and in vitro models, supporting the role of this emerging target. This review aims to illustrate the structure and biological function of HSP 90 in the context of IPF pathobiology, as well as perspective application of this molecule as a biomarker and therapeutic target for IPF."

Journal • Review • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • HSP90AA1 • TGFB1

Potential benefits of combined treatment with Hsp90 inhibitor AUY922 and cisplatin for overcoming drug resistance in nasopharyngeal carcinoma. (PubMed, Am J Cancer Res) - "These findings highlight the antiproliferative effects and anticancer activity of the AUY922/cisplatin combination in cisplatin-resistant NPC cells. The combination treatment of AUY922 and cisplatin holds promise as a strategy to overcome drug resistance in NPC patients."

Journal • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • ANXA5 • CDC37

Recent progress and structural insights of potential Hsp90 inhibitors as anticancer agents. (PubMed, Mol Divers) - "There are several heterocyclic small molecules under investigation in clinical studies, such as AUY922, SNX-5422, STA-9090, and others. This review also contained a patent of HSP90 inhibitors, which showed greater effectiveness. Therefore, the main objective of this paper is to summarize all recent developments in the creation of anticancer medications that target HSP90 inhibitors in order to treat anticancer disease."

Journal • Review • Oncology • CDC37

Identification and validation of mitochondria-related LncRNA signatures as a novel prognostic model for glioma. (PubMed, Anticancer Drugs) - "In addition, the high-risk group exhibited lower half-maximal inhibitory concentration values for specific chemotherapy medications, including bortezomib, luminespib, rapamycin, and 5-fluorouracil. Our study elucidates the diagnostic and prognostic value of mitochondria-related-lncRNAs in the promotion, suppression, and treatment of glioma."

Biomarker • Journal • Brain Cancer • CNS Tumor • Glioma • Metabolic Disorders • Oncology • Solid Tumor • CD8

Identification and validation of mitochondria-related LncRNA signatures as a novel prognostic model for glioma. (PubMed, Anticancer Drugs) - "In addition, the high-risk group exhibited lower half-maximal inhibitory concentration values for specific chemotherapy medications, including bortezomib, luminespib, rapamycin, and 5-fluorouracil. Our study elucidates the diagnostic and prognostic value of mitochondria-related-lncRNAs in the promotion, suppression, and treatment of glioma."

Journal • Brain Cancer • CNS Tumor • Glioma • Metabolic Disorders • Oncology • Solid Tumor • CD8

Autophagy Associated Genes (ARGs) -Based Predictive Model AIDPS for Prostate Cancer. (PubMed, J Cell Mol Med) - "We found significant differences in IC50 values of the Dactinomycin_1811, Dactolisib_1057, Luminespib_1559 and Paclitaxel_1080 between groups. In SNP sites rs2743987 and rs7768988, there was a significant correlation between prostate hyperplasia and prostate cancer. Our ARG-based predictive model AIDPS is a reliable and effective tool for prognosis and treatment of prostate cancer."

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

NVP-AUY922 relieves radiation-induced intestinal injury via regulating EPHX1. (PubMed, Life Sci) - "In addition, NVP-AUY922 could attenuate dextran sulfate sodium (DSS)-induced colitis and promote intestinal barrier recovery. Thus, our results suggest that NVP-AUY922 contributes to the amelioration of intestinal injury after radiation exposure, which offers a new approach for the prevention of RIII."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Respiratory Diseases • CDC37 • EPHX1

HSP90 Inhibitor AUY922 Suppresses Tumor Growth and Modulates Immune Response through YAP-TEAD Pathway Inhibition in Gastric Cancer. (PubMed, Cancer Lett) - "Our findings highlighted the suggestion of targeting HSP90 in GAC therapy via down-regulating YAP1/TEAD signaling. Additionally, our 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 • Journal • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • CDC37 • GZMB • IFNG • YAP1

A Novel Porphyromonas gingivalis Infection-Related Inflammatory Response-Related Genes Signature Predicts the Prognosis of Esophageal Squamous Cell Carcinoma. (PubMed, Clin Med Insights Oncol) - "A total of 41 drugs, including dactinomycin, luminespib, and sepantronium bromide, had a significant difference in IC50 between the 2 subgroups. We demonstrated the potential of a novel signature constructed from 4 P. gingivalis-related IRRGs for prognostic prediction in ESCC patients."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Infectious Disease • Oncology • Squamous Cell Carcinoma • DKK1 • EREG • ESRRB