Global Proteolysis Targeting Chimeras PROTAC Targeted Protein Degradation Therapy Clinical Trials Insight

Currently There Are More Than 50 PROTAC Drugs In Clinical Trials And Majority Are For Cancer As Per Recent Research Study By Kuick Research

/EIN News/ -- Delhi, Oct. 10, 2024 (GLOBE NEWSWIRE) -- Global Proteolysis Targeting Chimeras PROTAC Therapy Clinical Trials Insight & Market Opportunity Report Highlights:

• First PROTAC Drug Approval Expected By 2027
• Insight On More Than 50 PROTAC Drugs In Clinical Trials
• Global PROTAC Drugs Clinical Trials Insight By Company, Country, Indication & Phase
• Orphan & Fast Track Designation Insight
• PROTAC Drugs Clinical Application & Development Outlook By Indication
• Current & Future Market Overview
• Global PROTAC Drug Market Dynamics

Download Report: https://www.kuickresearch.com/ccformF.php?t=1728551968

Proteolysis-Targeting Chimeras (PROTACs) represent a revolutionary approach in targeted protein degradation therapy, offering a new strategy for treating diseases driven by aberrant proteins. Unlike traditional small-molecule inhibitors that suppress the activity of specific proteins, PROTACs eliminate these proteins altogether, addressing challenges posed by proteins considered "undruggable" by conventional methods. By exploiting the cell’s natural protein degradation system, PROTACs offer a powerful tool for treating conditions, particularly cancers, which are reliant on the presence and function of dysregulated proteins.

The mechanism behind PROTACs is built on their bifunctional structure. A PROTAC consists of two binding domains connected by a linker. One domain binds to the target protein, while the other binds to an E3 ubiquitin ligase. This enables the recruitment of the ubiquitin ligase to the target protein, facilitating the tagging of the protein with ubiquitin molecules. Once tagged, the protein is recognized by the proteasome, which degrades it. This mechanism allows for the complete removal of the target protein from the cell, unlike inhibitors that merely block its activity without affecting its levels.

One of the major advantages of PROTACs is their ability to address proteins that lack conventional binding sites for small-molecule drugs. Many proteins implicated in diseases like cancer do not have well-defined pockets or active sites where inhibitors can bind, making them difficult to target. PROTACs circumvent this limitation by focusing on protein degradation rather than inhibition. Since PROTACs do not require the traditional binding modes that inhibitors do, they can target proteins that were previously considered unreachable. This opens up new possibilities for targeting critical drivers of disease that were once classified as undruggable.

Another important feature of PROTACs is their catalytic mechanism. Traditional inhibitors require continuous binding to the target protein to suppress its function, which means that high concentrations of the inhibitor are often necessary to maintain efficacy. In contrast, PROTACs work catalytically, meaning they can induce the degradation of multiple molecules of the target protein with a single PROTAC molecule. Once the target protein has been ubiquitinated and degraded, the PROTAC is released and can go on to recruit additional molecules of the target protein for degradation. This catalytic nature enables PROTACs to be effective at lower doses than inhibitors, potentially reducing the risk of toxicity and side effects associated with high drug concentrations.

A notable application of PROTACs is in the treatment of cancers driven by overexpressed or mutated proteins. Many cancer therapies rely on inhibiting oncogenic proteins that promote cell growth and survival, such as kinases or transcription factors. However, these proteins often develop resistance to inhibitors through mutations that alter their binding sites. PROTACs offer a solution by degrading the entire protein, preventing it from contributing to the cancer’s progression regardless of mutations. For instance, PROTACs targeting mutated forms of the androgen receptor have shown promise in treating castration-resistant prostate cancer, a form of the disease that becomes resistant to standard therapies.

Beyond oncology, PROTACs are being explored for a wide range of other diseases, including neurodegenerative disorders, where misfolded or toxic proteins accumulate and cause cellular damage. In conditions like Alzheimer’s and Parkinson’s disease, the accumulation of such proteins is a key driver of pathology. PROTACs could offer a therapeutic strategy by promoting the degradation of these harmful proteins, potentially halting or slowing disease progression. The adaptability of PROTACs to target different types of proteins makes them an attractive option for addressing diverse diseases.

However, despite their potential, the development of PROTACs still faces challenges. One key challenge is ensuring selectivity, as off-target degradation of proteins could lead to unintended consequences, including toxicity or disruption of normal cellular functions. The design of PROTACs must ensure that they bind only to the intended target protein and that the selected E3 ubiquitin ligase is appropriately recruited for degradation. Additionally, the pharmacokinetics of PROTACs—how they are absorbed, distributed, metabolized, and excreted must be optimized to ensure they reach their target tissues and remain active for the desired duration.

Another challenge is the limited number of E3 ligases available for use in PROTAC design. While there are hundreds of E3 ligases in human cells, only a few are currently being utilized for therapeutic purposes. Expanding the repertoire of E3 ligases could enable more precise targeting and degradation of proteins across different cell types and disease contexts.

In conclusion, PROTACs represent a breakthrough in targeted protein degradation therapy, offering a novel solution to the limitations of traditional inhibitors. By removing disease-causing proteins entirely, PROTACs have the potential to treat a broad range of conditions, including cancers and neurodegenerative disorders. While challenges remain in their development, ongoing research is likely to overcome these hurdles, making PROTACs a critical component of future therapeutic strategies. As the field continues to evolve, PROTACs are poised to transform the landscape of drug development and disease treatment.

Neeraj Chawla
                    Research Head
                    Kuick Research
                    neeraj@kuickresearch.com
                    https://www.kuickresearch.com/