Design And Validation Of PROTAC Molecules For The Degradation Of Fibroblast Activated Protein（FAP）

Fibroblast activating protein（FAP）is overexpressed in tumor associated fibroblasts,which promotes tumor activity from many aspects,such as mechanism remodeling,angiogenesis,chemotherapy resistance and immunosuppression.FAP is selectively expressed on the surface of stromal fibroblasts of over 90% of epithelial malignancies,including breast cancer,ovarian cancer,lung cancer,colorectal cancer,and gastric cancer.Because the expression of FAP is very low in most normal organs and is not easy to mutate,it can be considered that FAP is a promising protein target for tumor therapy.One of the biggest advantages of this technology is that it can turn proteins into drug targets from "no drugs".Most small molecule drugs or monoclonal antibodies need to bind to the active sites of enzymes or receptors to play a role.However,80%of proteins in human cells lack such active sites.Protacs can grasp the target protein through any corner,so as to solve the problem of non drug of protein targets.PROTACs technology can be used to target a variety of proteins.Recently,this technology has attracted great attention from researchers in different fields,from cancer to neuronal diseases,because of its strong ability to induce the degradation of targeted proteins.The research content of this subject is to find and synthesize PROTAC that can effectively target the degradation of FAP through chemical synthesis technology and molecular biology technology.The research confirms the good targeted binding ability between UAMC-1110 and FAP.It is expected to inhibit tumor growth,improve inflammation and control the process of fibrosis through the degradation of FAP.