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PROTAC, also known as “PROteolysis-TArgeting Chimera,” is an emerging class of promising therapeutic small molecules. They are a heterobifunctional complex consisting of two terminal groups (ligand of the protein of interest (POI) and the particular ligand of E3 ubiquitin ligase) connected by a 5-15 atom linker. These molecules have potential advantages over conventional small molecule therapeutics as they are based on the concept of targeted protein degradation.

Targeted Protein Degradation (TPD):

Degradation of the target protein (Targeted Protein Degradation) is a new approach that has the potential to modulate disease indications and biological targets of interest that have historically been difficult to influence with conventional small molecules. PROTAC has been designed to degrade a variety of cancer and other disease target proteins, demonstrating promising profiles in a range of pre-clinical models and settings. This targeted protein degradation primarily eliminates proteins through the ubiquitin-proteasome and lysosome.

 

The image represents the degradation of targeted protein by Proteasome. Image source - https://www.phoremost.com/science

             (degradation of targeted protein by Proteasome. Image source – https://www.phoremost.com/science)

 

When compared to alternative therapies (such as cell therapy, antibody medicines, etc.), the synthesis and manufacture of PROTAC therapies are simpler. Hence it has the ability to modulate more challenging protein targets than many small-molecule drugs. As PROTAC provides a range of advantages over conventional drugs, this can result in superior efficacy.

Here are some of the advantages of PROTAC over conventional drugs:

 

Conventional drugs

 

PROTAC (Targeted Protein Degradation)

 

Modulate the function of a particular protein.

Degrades the targeted protein of interest (POI).

Constant target engagement is necessary in order to obtain the desired pharmacological effect.

Transient interactions might be sufficient to facilitate protein degradation.

Long-term overexposure may cause adverse effects through interaction with other proteins/biological targets.

More complex molecules tend to be more selective.

 

Overall, PROTACs represent a promising approach to drug development, with the potential to improve therapeutic outcomes for a variety of diseases.

In order for the two key proteins to be brought together and generate a suitable complex, the linker plays a pivotal role. Characteristics such as physicochemical properties, linker length, and attachment points can influence whether the complex can be formed in the first place and present the E3 ligase to the key lysine residues on the protein of interest to be ubiquitinated as a marker for protein destruction.

 

o2h discovery’s expertise in targeted protein degradation or PROTAC services:

o2h discovery is a leading drug discovery organisation that provides custom synthesis services. We have the capabilities to support hit-to-lead and lead optimisation programs to create novel IP and bring small molecules to the IND filing stage.

In the last few years, we have developed strong expertise in the synthesis and screening of complex PROTAC molecules, related specialty chemistry and PROTAC Services.

 

o2h discovery's expertise in Targeted protein degradation

                                               (o2h discovery’s expertise in Targeted protein degradation and PROTAC services)

 

We provide comprehensive solutions for designing and synthesis of PROTAC building blocks, linkers, compound libraries, and related intermediates to support Targeted Protein Degradation.

o2h discovery offers a range of E3 ligase ligands from an “off the shelf toolbox” for the quick synthesis of PROTAC equipped with a variety of linkers for quick assembly of degrader analogues to accelerate your drug discovery and development process. 

We also developed a range of analytical methods and purification protocols for the isolation of high-quality complex PROTAC molecules and their accurate characterization. Several building blocks have been prepared at gm scale with reliable synthetic routes and purification methodologies.

Here is a recent testimonial from one of our clients to whom we provided PROTAC services and helped their team to deliver a range of personalized, cutting-edge Targeted Protein Degradation/PROTAC services:

 

(Julian & Martin’s feedback about o2h discovery’s PROTAC/targeted protein degradation services)

To discover the full extent of the o2h toolbox offer please contact us at discovery@o2h.com

To know more about o2h discovery’s PROTAC services capabilities or to get a quote, please visit: https://o2h.com/protac-synthesis-services/

Also, check out our Integrated Drug Discovery Services, Chemistry, Biology, ADME, Scale Up and Specialty Chemistry services, and many more…


If you want to give a chemistry boost to your early-stage biotech, please read about our o2h Kickstarter competition (UK), o2h Kickstarter competition 2.0 (Australia), and o2h Kickstarter competition 3.0 (Israel)

For more information, visit o2h.com or contact us at: https://o2h.com/contact/


 

 

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