geldanamycin has been researched along with Lung-Neoplasms* in 4 studies
4 other study(ies) available for geldanamycin and Lung-Neoplasms
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Design, synthesis, and biological evalution of bifunctional inhibitors against Hsp90-HDAC6 interplay.
HDAC6 and Hsp90, existing as a cytosolic complex play an important role in maintaining the protein homeostasis. The interplay of HDAC6 and Hsp90 has attracted wide attention due to their important role and promise as therapeutic targets in malignant cancers. Therefore, the discovery of dual inhibitors targeting HDAC6 and Hsp90 is of high importance. In the present study, we describe the design, synthesis, and biological evaluation of bifunctional inhibitors against HDAC6 and Hsp90 interplay. In particular, compound 6e shows a significant inhibitory activity against both HDAC6 and Hsp90 with IC Topics: Animals; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Histone Deacetylase 6; Histone Deacetylase Inhibitors; HSP90 Heat-Shock Proteins; Humans; Lung Neoplasms | 2022 |
Ring-opening of five-membered heterocycles conjugated 4-isopropylresorcinol scaffold-based benzamides as HSP90 inhibitors suppressing tumor growth in vitro and in vivo.
Topics: Afatinib; Animals; Antineoplastic Agents; Benzamides; Cell Cycle Checkpoints; Cell Line; Cell Membrane Permeability; Cell Movement; Cell Proliferation; Drug Design; Drug Screening Assays, Antitumor; Drug Stability; ErbB Receptors; Half-Life; HSP90 Heat-Shock Proteins; Humans; Lung Neoplasms; Rats; Resorcinols; Transplantation, Heterologous | 2021 |
The antitumor agent PBT-1 directly targets HSP90 and hnRNP A2/B1 and inhibits lung adenocarcinoma growth and metastasis.
Natural products are the major sources of currently available anticancer drugs. We recently reported that phenanthrene-based tylophorine derivative-1 (PBT-1) may be a potential antitumor agent for lung adenocarcinoma. We therefore examined the direct targets of PBT-1 and their effects in inhibiting lung adenocarcinoma. We found that PBT-1 reduced the level of Slug and inhibits the migration, invasion, and filopodia formation of lung adenocarcinoma CL1-5 cells in vitro. In addition, PBT-1 displayed in vivo antitumor and antimetastasis activities against subcutaneous and orthotopic xenografts of CL1-5 cells in nude mice. Chemical proteomics showed that heat shock protein 90 (HSP90) and heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP A2/B1) bound PBT-1 in CL1-5 cells. Inhibition of HSP90 and hnRNP A2/B1 reduced the activation of AKT and Slug expression. Taken together, these findings suggest that PBT-1 binds to HSP90 and/or hnRNP A2/B1 and initiates antitumor activities by affecting Slug- and AKT-mediated metastasis and tumorigenesis. Topics: 8,11,14-Eicosatrienoic Acid; Adenocarcinoma; Adenocarcinoma of Lung; Animals; Antineoplastic Agents; Cadherins; Cell Line, Tumor; Cell Movement; Heterogeneous-Nuclear Ribonucleoprotein Group A-B; HSP90 Heat-Shock Proteins; Humans; Lung Neoplasms; Male; Mice; Mice, Nude; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Transplantation; Proto-Oncogene Proteins c-akt; Pseudopodia | 2014 |
Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor which significantly decreases tumor volume in a mouse xenograft model.
An extension of our previously reported series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. Addition of a second methyl group to the tether provided analogs that show increased potency in binding as well as cell-proliferation assays and, more importantly, are stable toward microsomes. We wish to disclose the discovery of a macrocycle which showed impressive biomarker activity 24-h post dosing and which demonstrated prolonged exposure in tumors. When studied in a lung cancer xenograft model, the compound demonstrated significant tumor size reduction. Topics: Administration, Oral; Animals; Antineoplastic Agents; Benzamides; Binding Sites; Biomarkers; Drug Evaluation, Preclinical; HSP90 Heat-Shock Proteins; Humans; Lung Neoplasms; Macrocyclic Compounds; Mice; Mice, Nude; Microsomes, Liver; Protein Structure, Tertiary; Rats; Transplantation, Heterologous | 2011 |