tanespimycin (BMS-722782)

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.

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.

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.

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.

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.

Subtype-dependent drug response profiles demonstrated sensitivity of AT/RT-SHH cell lines to B-cell lymphoma 2 (BCL2) and heat shock protein 90 (HSP90) inhibitors, and increased activity of microtubule inhibitors, kinesin spindle protein (KSP) inhibitors, and the eukaryotic translation initiation factor 4E (eIF4E) inhibitor briciclib in a subset of AT/RT-MYC cell lines. In summary, our in vitro pharmacogenomic approach revealed preclinical evidence of tumor type- and subtype-specific therapeutic vulnerabilities in AT/RT cell lines that may inform future in vivo and clinical evaluations of novel pharmacological strategies.

ZP3 has the potential to serve as a prognostic biomarker and therapeutic target for patients with PAAD.

Upon 1064 nm laser irradiation, USGRV-17-AAG exhibits a high photothermal conversion efficiency (65.1%) and thus can achieve temperature responsive release of tanespimycin (17-AAG), an inhibitor of HSP90...Additionally, USGRV-17-AAG exhibited efficient photothermal conversion (65.1%) under 1064 nm laser irradiation and enabled temperature-responsive drug release through the action of surface-modified upper critical solution temperature (UCST) polymers. This nanocarrier, with enhanced NIR-II photothermal therapy, might offer a promising solution for anti-tumor treatment.

PCSK1N is higher in SCA compared with FCA, and associated with corticotroph cell markers and tumor size. PCSK1N is likely to be part of the adaptive response to ER stress, potentially conferring a survival advantage to the corticotroph tumor cell in conjunction with other proteins.

Subsequently, chronic long-term exposure to the clinically advanced HSP90i PU-H71 (Zelavespib) led to copy number gain and mutation (p.S164F) of the HSP90AA1 gene, and HSP90α overexpression. In contrast, acquired resistance toward other tested HSP90i (Tanespimycin and Coumermycin A1) was attained by MDR1 efflux pump overexpression. Remarkably, combined CDK7 and HSP90 inhibition display synergistic activity against therapy-resistant BCR-ABL1+ patient leukemia cells via blocking pro-survival HSR and HSP90α overexpression, providing a novel strategy to avoid the emergence of resistance against treatment with HSP90i alone.

High CLIC1 expression samples were more sensitive to camptothecin, cisplatin, doxorubicin, erlotinib, paclitaxel, rapamycin, clofarabine, tanespimycin, methotrexate, everolimus, TAK-733, trametinib and AZD8330. Single-cell analysis unveiled that CLIC1 was expressed ubiquitously in tumor cells and tumor microenvironment. Overall, CLIC1 was a promising treatment vulnerability in glioma.

Consistent with this, in silico docking studies revealed that capsaicin binding to the ATP binding site of Hsp90 was distinct from classical N-terminus Hsp90 inhibitors, indicating a novel mechanism of action. Collectively, these findings support the use of capsaicin as a chemical scaffold to develop novel Hsp90 N-terminus inhibitors as well as its ability to be a potential cancer co-therapeutic.