PROTACs for Targeted Protein Degradation: Mechanisms, Design, and Controllable Delivery Strategies

Lukasz Misiak

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IJCRR - 17(18), September, 2025

Pages: 01-07

PROTACs for Targeted Protein Degradation: Mechanisms, Design, and Controllable Delivery Strategies

Author: Lukasz Misiak

Category: Healthcare

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Abstract:

Proteolysis-targeting chimeras (PROTACs) are an emerging class of bifunctional small molecules that induce targeted protein degradation by hijacking the cell’s ubiquitin–proteasome system. A PROTAC simultaneously binds a protein of interest (POI) and an E3 ubiquitin ligase, forming a ternary complex that leads to ubiquitination and proteasomal destruction of the target protein. Here, we present a concise review of PROTAC technology aimed at synthesizing recent advances in mechanism, molecular components, and rational design. Relevant literature was identified through searches of PubMed, Scopus, and Web of Sci ence up to August 2025. Articles were thematically analyzed to highlight mechanistic principles, structure–activity relationships, and delivery innovations. Evidence consistently shows that efficient degradation depends more on productive ternary-complex formation and cooperativity than on binary binding affinities, that linker geometry and E3 ligase choice are decisive factors for selectivity, and that new approaches such as photoswitchable PROTACs, pro-drug designs, and antibody or aptamer conjugates offer spatiotemporal control. The review concludes that standardization of cooperativity metrics, expansion to new E3 ligases, and integration with clinically validated targeting vectors are key priorities for future development.

Keywords: Linker design, Protein degradation, Cancer, Ligands, Clinical trial, Ubiquitin–proteasome system

DOI URL: https://doi.org/10.31782/IJCRR.2025.171801

Citation:

Lukasz Misiak. PROTACs for Targeted Protein Degradation: Mechanisms, Design, and Controllable Delivery Strategies International Journal of Current Research and Review. 17(18), September, 01-07

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A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for Vol 12 issue 08

A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for Vol 12 issue 07

A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20

A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR

A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13

A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR

A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR.

A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award

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PROTACs for Targeted Protein Degradation: Mechanisms, Design, and Controllable Delivery Strategies

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