ver-52296 has been researched along with Lung-Neoplasms* in 3 studies
3 other study(ies) available for ver-52296 and Lung-Neoplasms
| Article | Year |
|---|---|
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 |
Fluoropyrimidin-2,4-dihydroxy-5-isopropylbenzamides as antitumor agents against CRC and NSCLC cancer cells.
A major cause of failure of therapy in patients with non-small cell lung cancer (NSCLC) is development of acquired drug resistance leading to tumor recurrence and disease progression. In addition to the development of new generations of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), different molecular targets may provide opportunities to improve the therapeutic outcomes. In this study, we utilized the core structure 5-fluorouracil (5-FU) or tegafur, a 5-FU prodrug combined through different linkers with resorcinol to generate a series of fluoropyrimidin-2,4-dihydroxy-5-isopropylbenzamides which inhibit potent Heat Shock Protein 90 (HSP90). These compounds were found to show significant antiproliferative activity in colorectal cancer (CRC) HCT116 and NSCLC A549, H460, and H1975 (EGFR L858R/T790 M double mutation) cells. Compound 12c, developed by molecular docking analysis and enzymatic assays exhibits promising inhibitory activity of HSP90. This compound, 12c shows the most potent HSP90 inhibitory activity with an IC Topics: Antineoplastic Agents; Apoptosis; Benzamides; Carcinoma, Non-Small-Cell Lung; Caspases; Cell Line, Tumor; Colorectal Neoplasms; Cytoprotection; Enzyme Activation; ErbB Receptors; Humans; Inhibitory Concentration 50; Lung Neoplasms; Mutation; Proteolysis; Proto-Oncogene Proteins c-akt | 2020 |
Design, synthesis and pharmacological evaluation of 4,5-diarylisoxazols bearing amino acid residues within the 3-amido motif as potent heat shock protein 90 (Hsp90) inhibitors.
A structure-based medicinal chemistry optimization was conducted on the clinical Hsp90 inhibitor diarylisoxazole 3. Several series of new compounds were designed and synthesized by incorporating diversified amino acid derivatives with various lengths to the 3-amido motif of the isoxazole scaffold. Compound 14j was identified to have high Hsp90 binding potency (14 nM) and antiproliferative activity against H3122 human lung cancer and BT-474 breast cancer cells. Treatment of 14j with H3122 cell led to degradation of client protein ALK, reduction of downstream phosphorylation of AKT and ERK, and up-regulation of Hsp70. Molecular docking suggested that the terminal valine moiety and the ethyleneglycol linker in compound 14j formed additional apolar and polar interaction network with a number of amino acid residues. Topics: Amino Acids; Antineoplastic Agents; Breast; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Drug Design; Female; HSP90 Heat-Shock Proteins; Humans; Isoxazoles; Lung; Lung Neoplasms; Molecular Docking Simulation | 2017 |