초록 ▼

○종양세포의 Polo-like kinase 1(Plk1)의 병태생리적 의의를 기반으로 Plk1 PBD 타깃 분석법발굴 및 항암치료제 개발
-종양세포에 대한 Plk1의 PBD 타깃으로 하는 specific screening분석기술 확보
-Plk1의 PBD 타깃 특이성을 갖는 mono-specific inhibitor 및 높은 친화력의 펩타이드 개발하여 cell-based assay를 통해 종양세포의 Plk1에 의해 증식저해효과 검증
-종양발생에서 Plk1과 PBD 결합 단백질 발굴 및 protein-protein in

○종양세포의 Polo-like kinase 1(Plk1)의 병태생리적 의의를 기반으로 Plk1 PBD 타깃 분석법발굴 및 항암치료제 개발
-종양세포에 대한 Plk1의 PBD 타깃으로 하는 specific screening분석기술 확보
-Plk1의 PBD 타깃 특이성을 갖는 mono-specific inhibitor 및 높은 친화력의 펩타이드 개발하여 cell-based assay를 통해 종양세포의 Plk1에 의해 증식저해효과 검증
-종양발생에서 Plk1과 PBD 결합 단백질 발굴 및 protein-protein interaction의 규명
-종양세포 특이적인 Plk1 PBD타깃 분석법를 발굴하여 진단, 치료경과 추적/잔류병소검출
-새로운 표적치료 항암제 개발에 이용 및 항암합성물질의 최적화를 통한 약제 개발

Abstract ▼

○Purposes
- Development of chemical compounds of Plk1 inhibitors targeting Plk1 PBD in a wide spectrum of isogenic normal, cancer, and cancer stem cells to determine cancer cell selectivity
-Providing fundamental data for development of cancer therapeutic drugs and diagnostic kits targeting Pl

○Purposes
- Development of chemical compounds of Plk1 inhibitors targeting Plk1 PBD in a wide spectrum of isogenic normal, cancer, and cancer stem cells to determine cancer cell selectivity
-Providing fundamental data for development of cancer therapeutic drugs and diagnostic kits targeting Plk1 PBD
○Contents and results
- Potential Plk1 PBD inhibitors by carrying out high throughput screening against Plk1 PBD
- Establishment of quantification of Plk1 activity in cancer cells using ELISA and FP based Plk1 kinase assay:soluble GST-PBIPide containing the T78 motif
- Identification of cancer cell-selective Plk1 PBD-binding targets and understanding the molecular basis of these interactions in cancer cell
- Comparison of the activity of potential Plk1 PBD inhibitors in Plk1-dependent pathway(s) in cancer cells vs. normal cells
- Demonstration of inhibition of Plk1 PBD in the selective killing of cancer cells, not normal cells: Examination of selective killing effect of Plk1 PB inhibitors on cancer cells
- Profiling the patterns and mechanisms of tumor-cell kill for a given inhibitor and evaluation of potential combinatorial treatment with other known inhibitors with distinct pharmacological characters
○Expected contribution
- Validation of Plk1 as a biomarker for several types of human cancers and an important potential target for anti-cancer therapy
- Investigation of the mechanisms of how Plk1 deregulation leads to the development of cancers in humans
- Drug discovery based on strong basic science in eliminating suffering and death from cancer