dextromethorphan and Liver-Neoplasms
dextromethorphan has been researched along with Liver-Neoplasms* in 1 studies
Other Studies
1 other study(ies) available for dextromethorphan and Liver-Neoplasms
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Design, Synthesis, and Preclinical Evaluation of Fused Pyrimidine-Based Hydroxamates for the Treatment of Hepatocellular Carcinoma.
Class I histone deacetylases (HDACs) are highly expressed and/or upregulated in hepatocellular carcinoma (HCC) and are associated with aggressiveness, spread, and increased mortality of HCC. Activation of phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway was involved in the development of HCC and acquired resistance to sorafenib. A series of purine or 5H-pyrrolo[3,2-d]pyrimidine based hydroxamates were designed and developed as multitarget drugs to modulate both HDACs and the PI3K/Akt/mTOR pathway. Among 39 cell lines screened, the molecules (e.g., 20e, 20f, and 20q) were the most selective against leukemia, lymphoma, and HCC cells; they also demonstrated target modulation in cancer cell lines and in mice bearing MV4-11 and HepG2 tumors. Compound 20f in particular showed significant single agent oral efficacy in hypervascular liver cancer models (e.g., HepG2, HuH-7, and Hep3B) and was well-tolerated. These encouraging results, along with its favorable target profile and tissue distribution, warrant further development of 20f. Topics: Animals; Carcinoma, Hepatocellular; Cell Line, Tumor; Drug Screening Assays, Antitumor; Heterografts; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Liver Neoplasms; Liver Neoplasms, Experimental; Mice; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Pyrimidines; TOR Serine-Threonine Kinases; Xenograft Model Antitumor Assays | 2018 |