121st General Meeting of the KCS

Type Poster Presentation
Area Medicinal Chemistry
Room No. Event Hall
Time 4월 19일 (목요일) 11:00~12:30
Code MEDI.P-658
Subject Transglutaminase 2 Inhibitors towards The Treatment of Renal Cell Carcinoma (RCC)
Authors JiHee Kang, seri Bae, Minsoo Song1,*
Department of Chemistry, Daegu Gyeongbuk Medical Innovation Foundation, Korea
1Daegu Gyeongbuk Medical Innovation Foundation, Korea
Abstract Transglutaminase 2 (TGase 2, E.C. 2.1.2.13) is an enzyme that catalyzes an isopeptide bond between protein glutamine and lysine residues, resulting in a covalent crosslink. In renal cell carcinoma (RCC) cell lines, TGase 2 is highly overexpressed compared to normal cell lines and which deplete p53 into aggregates in autophagosome, leading to p53 depletion by the process of autophagy. This instability of p53 by TGase 2 regulation can cause tumor cells to avoid cell death and consequently have tumor cells grow. As such, the development of a new inhibitor of TGase 2 could be an effective strategy to treat RCC. In order to develop TGase 2 inhibitors, we have designed new type of scaffold of small molecule inhibitors for RCC. Over 250 compounds were synthesized and their biological activity were tested by in vitro enzyme assay and cell-based assay. Series of compounds were selected for ADME/T test and xenograft experiments. Among the tested compounds, we have identified that a lead compound DN201782 showed promising inhibitory efficacy both in vitro and in vivo against TGase 2. Herein, experimental data and xenograft results are presented in detail.
E-mail sswing2@dgmif.re.kr