• Bhavana Marri
• Malleswari Kunchala
• Desireddy Brahma Reddy

Proteolysis-targeting chimeras (PROTACs) represent an important approach within targeted protein degradation (TPD), where disease-associated proteins are selectively removed rather than merely inhibited. A typical PROTAC is a bifunctional molecule composed of a protein-of-interest (POI) ligand, a chemical linker and an E3 ubiquitin-ligase ligand. By bringing the target protein and an E3 ligase into proximity, the degrader promotes ubiquitination of the target, followed by recognition and proteolysis by the 26S proteasome. This event-driven mechanism distinguishes PROTACs from conventional occupancy-driven inhibitors and provides an opportunity to address proteins that are difficult to modulate by conventional approaches. The field has evolved from early peptide-based proof-of-concept molecules to small-molecule degraders using E3 ligases such as cereblon (CRBN) and von Hippel–Lindau (VHL), with increasing attention to ternary-complex formation, linker optimization, selectivity, pharmacokinetics and tissue exposure. PROTACs are being investigated particularly in oncology, including degradation of androgen receptor (AR), estrogen receptor (ER), Bruton's tyrosine kinase (BTK), BCR-ABL and other disease-associated proteins. Applications are also being explored in neurological, inflammatory, infectious and epigenetic disorders. Despite substantial progress, high molecular size, limited permeability, solubility and pharmacokinetic challenges, restricted E3-ligase availability, delivery barriers and acquired resistance remain important obstacles. Recent work is extending the field toward new E3 ligases, targeted delivery, conditional degraders, artificial-intelligence-assisted design and alternative degradation technologies. This review summarizes the principles, historical development, structural components, mechanism, design strategy, therapeutic applications, limitations, clinical development and future directions of PROTAC technology.

PROTACs; targeted protein degradation; ubiquitin–proteasome system; E3 ligase; CRBN; cancer therapy.

"A Review On Protac Technology : A New Strategy For Targeted Protein Degradation", International Journal of Emerging Technologies and Innovative Research (www.jetir.org), ISSN:2349-5162, Vol.13, Issue 10, page no.a521-a531, October-2026, Available :http://www.jetir.org/papers/JETIR2610057.pdf

"A Review On Protac Technology : A New Strategy For Targeted Protein Degradation", International Journal of Emerging Technologies and Innovative Research (www.jetir.org | UGC and issn Approved), ISSN:2349-5162, Vol.13, Issue 10, page no. ppa521-a531, October-2026, Available at : http://www.jetir.org/papers/JETIR2610057.pdf