Synthesis of bifunctional molecules for CERT degradation

Abstract

Cancer continues to be a leading global health problem being diagnosed each year to an important amount of people. There has been a lot of progress in cancer drug development, but the magnitude of cancer diseases requires a variety of therapeutic strategies. Many chemotherapeutic drugs act by increasing the synthesis of ceramides, pro-death signalling lipids. The transport of these ceramides from the endoplasmic reticulum to the Golgi apparatus for producing sphingomyelin is carried out by Ceramide Transfer Protein (CERT). CERT degradation causes ceramide accumulation, which is expected to sensitize cancer cells to drugs and to improve patient survival. Current pharmacological strategies to chemotherapeutics development involve proteolysis-targeting chimeras (PROTACs), which engage the ubiquitinproteasome system (UPS) to decrease protein levels. The general objective of this project is the synthesis of a PROTAC to induce the degradation of CERT