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Chemical Genetic Approaches to Screen Hypoxia-Modulating Agents and to Elucidate Their Action Mechanisms in Signaling Pathway

등록일
2005년 8월 11일 11시 09분 40초
접수번호
0755
발표코드
24P130포 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
발표시간
금 <발표Ⅰ>
발표형식
포스터
발표분야
생명화학
저자 및
공동저자
이우길, 박상은, 민용기, 김범태
한국화학연구원,
The adaptation of many multicellular organisms to dioxygen availability is mediated by hypoxia-inducible factor (HIF), which mediates cellular responses to low oxygen concentration via the transcriptional activation of specific genes involved in both tumorigenesis and angiogenesis. Today the manipulation of the HIF-1 pathway has the potential use to treat cancer and ischemic disease. To understand the hypoxia- signaling pathway using chemical genetic approach we developed the double readout cell-based assay system consisting of two stable cell lines. These reporter cell lines were mixed in a single well of 384-well plates and assayed for a KRICT chemical library RP set of 8,246 compounds in combination with the potent hypoxia inducing agent, CoCl2. As a result from HTS screening, several small molecules were found to inhibit hypoxia-mediated transcriptional activation and HIF-1a stabilization in very low concentration. Now we are attempting to elucidate their action mechanisms in hypoxia signaling pathway. These data suggest that our cell-based system provide the useful tool to screen and study the potential therapeutic agent to modulate the hypoxia pathway.

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