Chemically Induced Proximity (CIP)

HuProt for Chemically Induced Proximity

Many disease treatments target a specific protein with the goal of blocking it, activating it, or destroying it (often called targeted degradation). The challenge with this methodology is that most protein targets don’t have sites that conventional medicines can efficiently bind to, resulting in an estimation that only 15% of human proteins are “druggable” with conventional medicines. Multispecific medicines overcome this challenge by using the principle of chemically induced proximity (CIP), in which they bring two things together, by using small molecules or chemical ligands. CIP is a powerful approach used in chemical biology and drug discovery to modulate protein function through the controlled assembly of protein complexes. CIP technologies, such as PROTACs (PROteolysis TArgeting Chimeras), LYTACs (LYsosome TArgeting Chimeras), and AUTOTACs (AUTOphagy- TArgeting Chimeras), leverage small molecules to induce the proximity of target proteins with specific cellular components, leading to their degradation or modification.

The featured publication below outlines that the identification of protein substrates of ubiquitin E3 ligases in genetic/cellular experiments is challenging because of the complex milieu of the cell, the hundreds of E3 ligases present, and the potential for many indirect effects associated with loss- or gain-of-function of a particular enzyme. HuProt™ microarray technology was highlighted as offering an attractive alternative to standard cellular experiments because its application can rapidly and directly assess proteome wide enzyme-substrate relationships, even for low abundance proteins.