• 제목/요약/키워드: Chemical genomics

검색결과 145건 처리시간 0.023초

Synergistic antitumor activity of sorafenib and MG149 in hepatocellular carcinoma cells

  • Moon, Byul;Park, Mijin;Cho, Seung-Hyun;Kim, Kang Mo;Seo, Haeng Ran;Kim, Jeong-Hoon;Kim, Jung-Ae
    • BMB Reports
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    • 제55권10호
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    • pp.506-511
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    • 2022
  • Advanced hepatocellular carcinoma (HCC) is among the most challenging cancers to overcome, and there is a need for better therapeutic strategies. Among the different cancer drugs that have been used in clinics, sorafenib is considered the standard first-line drug for advanced HCC. Here, to identify a chemical compound displaying a synergistic effect with sorafenib in HCC, we screened a focused chemical library and found that MG149, a histone acetyltransferase inhibitor targeting the MYST family, exhibited the most synergistic anticancer effect with sorafenib on HCC cells. The combination of sorafenib and MG149 exerted a synergistic anti-proliferation effect on HCC cells by inducing apoptotic cell death. We revealed that cotreatment with sorafenib and MG149 aggravated endoplasmic reticulum (ER) stress to promote the death of HCC cells rather than adaptive cell survival. In addition, combined treatment with sorafenib and MG149 significantly increased the intracellular levels of unfolded proteins and reactive oxygen species, which upregulated ER stress. Collectively, these results suggest that MG149 has the potential to improve the efficacy of sorafenib in advanced HCC via the upregulation of cytotoxic ER stress.

Toxicoinformatics: The Master Key for Toxicogenomics

  • Lee, Wan-Sun;Kim, Yang-Seok
    • Molecular & Cellular Toxicology
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    • 제1권1호
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    • pp.13-16
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    • 2005
  • The current vision of toxicogenomics is the development of methods or platforms to predict toxicity of un characterized chemicals by using '-omics' information in pre-clinical stage. Because each chemical has different ADME (absorption, distribution, mechanism, excretion) and experimental animals have lots of variation, precise prediction of chemical's toxicity based on '-omics' information and toxicity data of known chemicals is very difficult problem. So, the importance of bioinformatics is more emphasized on toxicogenomics than other functional genomics studies because these problems can not be solved only with experiments. Thus, toxicoinformatics covers all information-based analytical methods from gene expression (bioinformatics) to chemical structures (cheminformatics) and it also deals with the integration of wide range of experimental data for further extensive analyses. In this review, the overall strategy to toxicoinformatics is discussed.

WebChemDB: An Integrated Chemical Database Retrieval System

  • Hou, Bo-Kyeng;Moon, Eun-Joung;Moon, Sung-Chul;Kim, Hae-Jin
    • Genomics & Informatics
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    • 제7권4호
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    • pp.212-216
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    • 2009
  • WebChemDB is an integrated chemical database retrieval system that provides access to over 8 million publicly available chemical structures, including related information on their biological activities and direct links to other public chemical resources, such as PubChem, ChEBI, and DrugBank. The data are publicly available over the web, using two-dimensional (2D) and three-dimensional (3D) structure retrieval systems with various filters and molecular descriptors. The web services API also provides researchers with functionalities to programmatically manipulate, search, and analyze the data.