onalespib (AT13387) / Otsuka 
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 26 Diseases   5 Trials   5 Trials   175 News 


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  • ||||||||||  aminoflavone Prodrug (AFP-464) / Kirax, onalespib (AT13387) / Otsuka
    Biomarker, Journal, Tumor mutational burden, Pan tumor:  Systematic pan-cancer analysis identifies cGAS as an immunological and prognostic biomarker. (Pubmed Central) -  Feb 23, 2023   
    This study discovered that SARS-CoV-2-infected cancer patients might experience changes in their tumor environment as a result of cGAS, making patients with tumors expressing high cGAS more susceptible to COVID-19 and possibly a worsening prognosis. Furthermore, cGAS may be a novel biomarker for diagnosing and treating COVID-19-infected tumor patients.
  • ||||||||||  zelavespib intravenous (PU-H71 IV) / Samus Therap, onalespib (AT13387) / Otsuka
    Preclinical, Journal:  Radiosynthesis and preclinical evaluation of [C]SNX-ab as an Hsp90α,β isoform-selective PET probe for in vivo brain and tumour imaging. (Pubmed Central) -  Jan 31, 2023   
    Our results suggest that [C]SNX-ab is not an ideal probe for in vivo visualization and quantification of Hsp90α/β expression levels in tumour and brain. Future research in the development of next-generation Hsp90 isoform-selective PET tracers is warranted to dissect the role played by each isoform towards disease pathology and support the development of subtype-specific Hsp90 therapeutics.
  • ||||||||||  onalespib (AT13387) / Otsuka
    Trial termination, Combination therapy, Metastases:  Onalespib and Paclitaxel in Treating Patients With Advanced Triple Negative Breast Cancer (clinicaltrials.gov) -  Nov 4, 2022   
    P1b,  N=31, Terminated, 
    Future research in the development of next-generation Hsp90 isoform-selective PET tracers is warranted to dissect the role played by each isoform towards disease pathology and support the development of subtype-specific Hsp90 therapeutics. Active, not recruiting --> Terminated; Drug supply issues
  • ||||||||||  SP600125 / BMS, onalespib (AT13387) / Otsuka
    Journal:  Upregulation of TGF-β-induced HSP27 by HSP90 inhibitors in osteoblasts. (Pubmed Central) -  Jun 4, 2022   
    Our results strongly suggest that HSP90 inhibitors reduce the EGF-induced osteoblast migration through the p44/p42 MAP kinase. Our results strongly suggest that HSP90 inhibitors upregulated the TGF-β-induced HSP27 expression and that these effects of HSP90 inhibitors were mediated through SAPK/JNK pathway in osteoblasts.
  • ||||||||||  Lynparza (olaparib) / Merck (MSD), AstraZeneca, onalespib (AT13387) / Otsuka
    P1 data, Preclinical, Journal, BRCA Biomarker, PARP Biomarker:  Combined PARP and HSP90 inhibition: preclinical and Phase 1 evaluation in patients with advanced solid tumours. (Pubmed Central) -  Apr 7, 2022   
    These data suggest that spike protein subunit 1 can elicit, by itself, direct injury to the endothelium and suggest a role of HSP90 inhibitors in preserving endothelial functionality. Combining onalespib and olaparib was feasible and demonstrated preliminary evidence of anti-tumour activity.
  • ||||||||||  onalespib (AT13387) / Otsuka
    Antidotal Effects of the HSP90 Inhibitor, AT13387, Against Exposure to HCl in Adult and Pubescent Mice (Room 203-204 (South Building, Level 2), Moscone Center) -  Feb 19, 2022 - Abstract #ATS2022ATS_4078;    
    We conclude that AT13387 can be administered subcutaneously in pre-hospital settings or in the field and due to its safe profile, anti-inflammatory properties and modulative effects on TGF-β signaling, is a promising drug candidate for chronic lung injury after chemical exposures. Supported by U01ES030674
  • ||||||||||  onalespib (AT13387) / Otsuka
    Trial primary completion date, Combination therapy, Metastases:  Onalespib and Paclitaxel in Treating Patients With Advanced Triple Negative Breast Cancer (clinicaltrials.gov) -  Jan 6, 2022   
    P1b,  N=33, Active, not recruiting, 
    Their chemical structures are simpler, and they are likely to exhibit lower side effects than the much more complex inhibitors used as controls. Trial primary completion date: Dec 2021 --> Dec 2022
  • ||||||||||  cisplatin / Generic mfg.
    Journal:  HSP90 Inhibition Synergizes with Cisplatin to Eliminate Basal-like Pancreatic Ductal Adenocarcinoma Cells. (Pubmed Central) -  Dec 27, 2021   
    Here again, when treating established tumors, the combination of cisplatin with the HSP90 inhibitor onalespib was highly effective and almost completely prevented further tumor growth. We propose that the combination of platinum drugs and HSP90 inhibitors might be worth testing in the clinics for the treatment of cisplatin-resistant PDACs.
  • ||||||||||  onalespib (AT13387) / Otsuka
    Journal:  Low dose Hsp90 inhibitor selectively radiosensitizes HNSCC and Pancreatic xenografts. (Pubmed Central) -  Nov 29, 2021   
    The current study shows that a significant therapeutic ratio can be achieved by a low dose of Hsp90 inhibitor in combination with radiotherapy. Hsp90 inhibition, even at a low dose, can be monitored by measuring Hsp70 expression in PBMC in human studies.
  • ||||||||||  onalespib (AT13387) / Otsuka
    MYC generates aggressive medulloblastoma by HSP90 pathway activation and ARF silencing (Exhibit Hall D) -  Nov 16, 2021 - Abstract #SNO2021SNO_953;    
    The HSP90 inhibitor Onalespib showed significant selectivity for targeting MYC-driven as compared to MYCN-driven tumors. The drug promoted ARF restoration and increased the survival in our animal model which suggests that it could be potentially used in the treatment of MYC-driven ARF-silenced brain cancer patients.
  • ||||||||||  temozolomide / Generic mfg.
    [VIRTUAL] Oncogenic chaperoning of Hsp90 in glioma with FGFR3-TACC3 (Channel 1) -  Aug 20, 2021 - Abstract #EANO2021EANO_4;    
    F3-T3 is a strong Hsp90 client that shows strong addiction to the Hsp90-Cdc37 chaperone system. Combination therapy with Hsp90 inhibitor overcomes the TMZ resistance conferred by F3-T3.
  • ||||||||||  ganetespib (ADX-1612) / Aldeyra, onalespib (AT13387) / Otsuka
    Journal:  The Gain-of-Function p53 R248W Mutant Promotes Migration by STAT3 Deregulation in Human Pancreatic Cancer Cells. (Pubmed Central) -  Jun 29, 2021   
    The selective mutp53 GOF signals through enhancing the STAT3 axis, which was confirmed since targeting STAT3 by knockdown or pharmacological inhibition phenocopied mutp53 depletion and reduced cell viability and migration preferentially in mutp53-containing PDAC cells. Our results confirm that mutp53 GOF activities are allele specific and can span across tumor entities.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  HSP90 inhibitors strengthen extracellular ATP-stimulated synthesis of interleukin-6 in osteoblasts: Amplification of p38 MAP kinase. (Pubmed Central) -  Jun 3, 2021   
    Geldanamycin, 17-allylamino-17-demethoxy-geldanamycin (17-AAG) and onalespib, three different HSP90 inhibitors, amplified the ATP-stimulated IL-6 release...Inhibitors of MEK1/2 (PD98059), JNK (SP600125), upstream kinase of p70 S6 kinase (rapamycin) and Akt (deguelin), all increased IL-6 release...In the present study, we investigated whether HSP90 is implicated in extracellular ATP-induced interleukin (IL)-6 synthesis in osteoblast-like MC3T3-E1 cells. Our results strongly suggest that HSP90 inhibitors up-regulate extracellular ATP-stimulated IL-6 synthesis via amplification of p38 mitogen-activated protein kinase activation in osteoblasts.
  • ||||||||||  onalespib (AT13387) / Otsuka
    Enrollment change, Trial termination, Trial primary completion date:  Phase 2 Study of AT13387 (Onalespib) in ALK+ ALCL, MCL, and BCL-6+ DLBCL (clinicaltrials.gov) -  Mar 22, 2021   
    P2,  N=25, Terminated, 
    Utilizing Onalespib's radiosensitizing properties with Lu-DOTATATE may lead to better therapeutic results in the future and may reduce unwanted side effects in dose-limiting organs. N=50 --> 25 | Active, not recruiting --> Terminated | Trial primary completion date: Oct 2021 --> Mar 2021; Drug supply issues
  • ||||||||||  onalespib (AT13387) / Otsuka
    Journal:  Overcoming Limitations of Cisplatin Therapy by Additional Treatment With the HSP90 Inhibitor Onalespib. (Pubmed Central) -  Oct 28, 2020   
    The results of this study demonstrate that the reduced therapeutic efficacy of cisplatin due to drug-resistance could be overcome by combination treatment with onalespib. We speculate that the increased apoptotic signaling, DNA damage as well as the downregulation of HSP90 client proteins are important mechanisms promoting increased sensitivity to cisplatin treatment.
  • ||||||||||  Q-Force (quercetin) / Quercegen, Temple University
    [VIRTUAL] Novel therapy to target pr-recurrent glioma () -  Oct 24, 2020 - Abstract #SNO2020SNO_823;    
    Background: Glioblastoma is a fatal infiltrative primary brain tumor, and standard care includes maximal safe surgical resection followed by radiation and Temozolomide (TMZ)...We evaluated the IC50 for several senolytics targeting multiple SCAPs, including Dasatinib, Quercetin, AMG-232, Fisetin, Onalespib, Navitoclax, and A1331852, and in senescent vs. proliferating cells... These findings suggest the potential to harness radiation-induced biology to ablate surviving quiescent cells and demonstrate Bcl-XL dependency as a potential vulnerability of surviving tumor cells after exposure to chemoradiation.