Targeted protein degraders (TPD) are a new class of therapeutic drugs, which may solve the problem of drug targeting in a new way. Targeted protein degradation agents - including molecular gels and heterobifunctional molecules - are a rapidly developing class of drugs with potential for cancer and other diseases.
Protein degradation targeted chimeric Technology (PROTAC) uses heterobifunctional small molecular compounds to bring the target protein closer to the E3 ligase in cells, and specifically degrades the target protein by using the ubiquitin proteasome protein degradation pathway in vivo. PROTAC molecule is composed of three parts, one end is a specific E3 ligase ligand, the other end is a specific ligand of the target protein, and the middle linker, so as to form a "target protein protac-e3 ligase" ternary complex.
At present, a variety of strategies have been developed for cancer treatment, such as small molecule inhibitors, monoclonal antibodies, RNA interference and CRISPR/Cas9; Due to its unique chemical and biological characteristics, PROTAC has unique advantages and disadvantages in cancer treatment. The advantages of PROTAC include: event driven activity, targeting non pharmaceutical proteins, overcoming traditional drug resistance, etc. Disadvantages include membrane permeability, off target toxicity, etc.
From the perspective of targets, according to the latest statistics in December 2021, more than 130 PROTAC targets have been reported, and the number of degradable targets reported from 2020 to 2021 (about 90) has completely exceeded the total amount of the previous 18 years, indicating that the era of protein degradation is coming.
In the reported studies, researchers prefer to choose kinase as the target of protein degradation. According to incomplete statistics, about 54 kinases can be degraded by protein degrading agents based on PROTAC. At present, 518 kinases have been found. According to the classification of human kinase map, Creative BioMart provides the kinases that can be degraded as "degradable kinases" below. In the "degradable" kinase table, according to the classification method of kinase map, only CK1 and CaMK kinase groups have not reported related PROTAC. RTKs and CMGCS kinases have been reported to have the most degradable targets, 19 and 14, respectively, accounting for more than half of the total number of degradable kinases.
Besides the PROTAC targets, E3 ligases is also important for PROTAC. Only a relatively small number of E3 ligases out of the >600 E3 ligases encoded by human genomes have been exploited by small molecules for TPD applications.
To support PROTAC research and therapeutics, Creative BioMart provides our customers with a list of recombinant E3 proteins to effectuate TPD.
Can't find what you are looking for exactly? We can still help! Creative BioMart has focused on protein production and purification for years, and our custom-service team is capable of creating the protein that suits your experimental needs.
What else? We can also provide PROTACs services, including:
- E3 ligase and target protein development service
- Ligand discovery and design service
- PROTAC in vitro evaluation
- PROTAC in vivo evaluation
- Targeted protein degradation service