- |||||||||| Lynparza (olaparib) / Merck (MSD), AstraZeneca, onalespib (AT13387) / Otsuka
Trial completion, Surgery, Metastases: Olaparib and Onalespib in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple-Negative Breast Cancer (clinicaltrials.gov) - Apr 26, 2023 P1, N=28, Completed, > Active, not recruiting --> Completed
- |||||||||| 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.
- |||||||||| 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.
- |||||||||| onalespib (AT13387) / Otsuka
Journal: The Heat Shock Protein 90 Inhibitor, AT13387, Protects the Alveolo-Capillary Barrier and Prevents HCl-Induced Chronic Lung Injury and Pulmonary Fibrosis. (Pubmed Central) - Apr 13, 2022 In vitro, AT13387 prevented HCl-induced loss of barrier function and AKT, ERK, and ROCK1 activation, and restored HSP70 and cofilin expression. The HSP90 inhibitor, AT13387, represents a promising drug candidate for chronic lung injury that can be administered subcutaneously in the field, and at low, non-toxic doses.
- |||||||||| 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
- |||||||||| Lynparza (olaparib) / Merck (MSD), AstraZeneca, onalespib (AT13387) / Otsuka
Enrollment change, Trial completion date, Surgery, Metastases: Olaparib and Onalespib in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple-Negative Breast Cancer (clinicaltrials.gov) - Dec 10, 2021 P1, N=28, Active, not recruiting, 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. N=40 --> 28 | Trial completion date: Dec 2021 --> Dec 2022
- |||||||||| 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.
- |||||||||| 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
- |||||||||| Lynparza (olaparib) / Merck (MSD), AstraZeneca, onalespib (AT13387) / Otsuka
Trial completion date, Trial primary completion date, Surgery, Metastases: Olaparib and Onalespib in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple-Negative Breast Cancer (clinicaltrials.gov) - Dec 16, 2020 P1, N=40, Active, not recruiting, Thus, individually, or in combination with radiotherapy Onalespib inhibits tumor growth and has the potential to improve radiotherapy outcomes, prolonging the overall survival of cancer patients. Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Dec 2021
- |||||||||| AT7519 / Novartis, Otsuka, onalespib (AT13387) / Otsuka
Enrollment closed, Surgery, Metastases: Onalespib and CDKI AT7519 in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov) - Nov 16, 2020 P1, N=29, Active, not recruiting, Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Dec 2021 Completed --> Active, not recruiting
- |||||||||| 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.
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