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제123회 대한화학회 학술발표회, 총회 및 기기전시회 안내 The Development and lead Optimization of Transglutaminase 2 Inhibitors for the Treatment of Renal Cell Carcinoma (RCC).

2019년 2월 14일 15시 13분 34초
MEDI.P-419 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
4월 18일 (목요일) 11:00~12:30
Medicinal Chemistry
저자 및
Eun Bi Ko, Chunyoung Im, Ga Young Park, JiHee Kang, Eunhye Lee, Soong-Hyun Kim, Minsoo Song*
New Drug Development Center, Daegu Gyeongbuk Medical Innovation Foundation, Korea
Renal cell carcinoma (RCC) is the most common malignant tumor of the human kidney. In RCC cell lines, Transglutaminase 2 (TGase 2, E.C., a protein cross-linking enzyme, is considerably over-expressed in comparison to the level of TGase 2 expression in normal kidney. TGase 2 in RCC binds directly to p53 and induces p53 depletion by the process of autophagy, consequently RCC surviving from p53-induced apoptosis. Therefore, hindering RCC growth via inhibition of TGase 2 could be an effective strategy to treat RCC. In order to develop new inhibitors of TGase 2, we designed small molecule inhibitors of TGase 2. Over 250 compounds were synthesized and the biological activity of the compounds was determined by in vitro enzyme assay and cell-based assay. Through our SAR analysis, several compounds are identified as highly potent TGase 2 inhibitors. Series of compounds were selected for ADME/T test and xenograft experiments. As a result, we have found compound DN201782 as a lead compound with in vitro and in vivo efficacy. That could be applied to potential therafeutic agent for treating RCC.Herein, experimental data and xenograft results are presented in detail.