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-624
Subject Development of novel scaffold for Focal adhesion kinase and Fms like tyrosine Kinase 3 dual inhibitor
Authors Hanna Cho, Injae Shin1, Taebo Sim2,*
KU-KIST Graduate School of Converging Science and Technology, Korea University, Korea
1Korea University, Korea
2Chemical Kinomics Research Center, Korea Institute of Science and Technology, Korea
Abstract Focal adhesion kinase (FAK) plays central role in building focal adhesion associating with cell attachment and signal transduction. FAK is elaborately controlled and dysregulated FAK causes tumorigenesis and metastasis phenotype. In highly invasive and metastatic human cancers, hyper activation or elevated expression of FAK are founded. Thus, targeting FAK kinase domain has been regarded promising strategy to treat cancers bearing malfunctioned FAK. Here, we discovered a new scaffold and synthesized 28 derivatives for developing FAK inhibitor. Through SAR study within biochemical assay and constitutively activated FAK-transformed Ba/F3 system, we identified compound 10 exhibiting great potency against recombinant FAK and Ba/F3-FAK cell. In the in vivo studies using MDA-MB-231 cells-inoculated xenograft and orthotopic mouse model, 10 demonstrated a good bioavailability and significant suppression of the tumor growth and metastasis without appreciable toxicity. These data collectively support the potential of 10 to be an effective treatment for FAK-deregulated metastatic cancers.
E-mail 214844@kist.re.kr