Is Protein An Enzyme? Understanding Targeted Protein Degradation Drugs

Targeted protein degradation (TPD) technology is a new technology that specifically identifies target proteins and directly degrades them using intrinsic intracellular protein degradation pathways. Currently, the field of TPD has developed technologies such as PROTAC, molecular gels, degradation tags, lysosomal targeting chimeras, and autophagic vesicle-binding compounds, which greatly expand the range of degradable target proteins. Do you know about is protein an enzyme?

Recently, Jiangsu-based Medinocon announced the completion of an angel round of financing of nearly 100 million RMB. The funding in this round will be mainly used for the expansion and application of two Targeted Protein Degradation (TPD) platforms to advance the development of several oncology and tumor immunology drug pipelines.Scientists are studying it is protein an enzyme.

TPD is a hot area for new drug discovery and development. Currently, a number of companies, universities or R&D institutions around the world are conducting TPD drug development. More and more companies in China are also joining in the R&D of TPD drugs.

Proteins, which form the basis of all living things including human beings, are constantly produced and die in living organisms.

Most diseases are associated with abnormal expression or activity of proteins, and selective elimination of disease-causing proteins will facilitate the cure of diseases.Some scientific experiments on what is protein an enzyme.

Currently, the vast majority of drugs are protein inhibitors, which inhibit the activity of disease-causing proteins by binding specifically to them in order to obtain efficacy. However, the number of disease-causing proteins that can be bound by inhibitors is currently limited, less than 20% of the total number of potential disease-causing proteins, and 80% of the disease-causing proteins are non-druggable targets.

In the 1970s and 1980s, Israeli scientists Alon Cichanova and Avram Hershko and American scientist Irwin Roth discovered ubiquitin-mediated protein degradation after years of research. They were awarded the Nobel Prize in 2004 for this work.

Ubiquitin is a polypeptide consisting of 76 amino acids that form strong covalent bonds with proteins, and once tagged with it, proteins are sent to the proteasome, an intracellular "waste treatment plant," for degradation.

TPD technology is a new technology that specifically identifies target proteins and uses the inherent intracellular protein degradation pathway to directly degrade them. This is equivalent to finding the disease-causing "targets" inside the cells and eradicating them.Some scientific progress has been made in what is protein an enzyme.

"TPD drugs borrow from the cell's own ubiquitin-proteasome system (UPS) to get rid of the disease-causing proteins." Dr. Xie Weilin, founder of Medinocon, further explained.

The concept of targeted protein degradation was first introduced in 1999. in 2001, scholars proposed a more specific concept of protein degradation targeted chimeras (PROTAC) and synthesized the first chimeric molecule targeting protein degradation. in 2013, Arvinas, the first public company in the field of PAOTAC, was born.

Zhiyu Li, a professor at China Pharmaceutical University, told reporters, "PROTAC is a novel drug molecule that allows target proteins to come close to E3 ubiquitin ligases, be ubiquitously labeled, and have the target proteins recognized and degraded by the proteasome."

Currently, the field of TPD has developed technologies such as PROTAC, molecular gels, degradation tags, lysosome-targeted chimeras, and autophagic vesicle-bound compounds, which have greatly expanded the range of degradable target proteins.

Experts say that there are about 600 types of E3 ubiquitin ligases, and in order to prevent the emergence of drug resistance in CRBN, there is a need to discover more E3 ubiquitin ligases that can be applied and widely distributed in the human body to enrich the "toolbox" of TPD.

It is encouraging to note that Dialectic Therapeutics' BCL-xL degrader DT2216, which uses VHL as an E3 ubiquitin ligase, is currently in Phase I clinical trials as research progresses. In addition, TPD drugs utilizing E3 ubiquitin ligases such as MDM2, RNF14, β-TRCP, clAP, RNF, and DCAF16 are also in development.

While the development boom of TPD drugs is roaring, there is an urgent need to establish validation standards and guidelines for the drugs. Zhiyu Li pointed out that many proteins have physiological functions, and it is difficult to predict what negative effects will be brought to the human body by removing the whole protein; secondly, the synthesis of TPD drugs such as PROTAC is complex, slow and costly to develop, and the synthesis steps need to be optimized.