PROTAC technology

The PROTAC drug discovery technology summarizes the current popular target protein ligand; A wide range of popular targeted protein high affinity small molecule and small molecule fragment compound library (TPSM), a wide range of E3 ligase, high affinity small molecule and small molecule fragment (E3SM) have been established. A linker system was established, including the collection of a large number of bifunctional connectomes with a wide diversity (BF-Linker). These accumulated compound libraries can help the rapid and efficient synthesis of a large number of highly active PROTAC bispecific small molecules, and greatly improve the drug development process using PROTAC technology. In addition to rapid synthesis, we also established and improved the PROTAC biological screening and testing platform, which was subsequently developed to all stages of preclinical development until the drug was finally marketed.

Mechanism of action of PROTAC technique

 1. PROTAC molecule specifically recognizes and binds to target proteins through POI Ligand at one end and E3 ubiquitin Ligase Ligand at the other end.

 2. Form POI-PROTAC-E3 ligase ternary complex.

 3. The target protein POI is ubiquitinated by E3 ligase in this triplex complex, and the ubiquitinated POI is subsequently recognized and degraded by the proteasome, thereby inhibiting the function of the target protein.

PROTAC technology advantages

Change the druggability of the target

The molecular mechanism of action of PROTAC is to degrade the target protein through the ubiquitin-proteasome system, and does not exert protein function inhibition by competing for binding to block the target protein functional region, so PROTAC does not necessarily have to be an active region for the target protein recognition binding region, and the binding force does not necessarily have to be high affinity; This makes some "undruggable" target proteins that lack high affinity small molecule binding become "druggable".

High efficiency

Traditional small molecule inhibitors inhibit target protein function by competing for binding to the active functional domain of the target protein. The amount of PROTAC is often large; however, PROTAC degrades the target protein through the ubiquitin-proteasome system to remove the function of the target protein, so it has the characteristics of recyclability, low dosage and high efficiency.