PROTAC Delivery Strategies for Overcoming Physicochemical Properties and Physiological Barriers in Targeted Protein Degradation

Syahputra, Endry Wahyu; Lee, Hyunji; Cho, Hyuk Jun; Park, Hyun Jin; Park, Kwang‐Su; Hwang, Duhyeong

doi:10.3390/pharmaceutics17040501

reviewPharmaceuticsApr 9, 2025GOLD OA

PROTAC Delivery Strategies for Overcoming Physicochemical Properties and Physiological Barriers in Targeted Protein Degradation

EWEndry Wahyu Syahputra HLHyunji Lee HJHyuk Jun Cho HJHyun Jin Park KPKwang‐Su Park

Keimyung University · Kyungsung University

PubMed

Indexed incrossrefdoajpubmed

Abstract

Proteolysis targeting chimeras (PROTACs), heterobifunctional molecules that hijack the ubiquitin-proteasome system (UPS) to degrade specific proteins, hold great promise in treating diseases driven by traditionally "undruggable" targets. However, their large molecular weight, high hydrophobicity, and other physicochemical hurdles contribute to their limited bioavailability, suboptimal pharmacokinetics, and attenuated therapeutic efficacy. Consequently, diverse formulation innovations have been investigated to optimize PROTAC delivery. This review examines current challenges and advances in specialized drug delivery approaches designed to bolster PROTAC pharmacological performance. We first outline the…

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47

total citations

FWCI: 29.40
Percentile: 100%
References: 119

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6

Topics & keywords

Topics

Keywords

Drug delivery
Nanotechnology
Nanomedicine
Liposome
Cell permeability
Druggability
Chemistry
Materials science

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