TY - JOUR
T1 - Peptide–Drug Conjugates as Next-Generation Therapeutics
T2 - Exploring the Potential and Clinical Progress
AU - Jadhav, Krishna
AU - Abhang, Ashwin
AU - Kole, Eknath B.
AU - Gadade, Dipak
AU - Dusane, Apurva
AU - Iyer, Aditya
AU - Sharma, Ankur
AU - Rout, Saroj Kumar
AU - Gholap, Amol D.
AU - Naik, Jitendra
AU - Verma, Rahul K.
AU - Rojekar, Satish
N1 - Publisher Copyright:
© 2025 by the authors.
PY - 2025/5
Y1 - 2025/5
N2 - Peptide–drug conjugates (PDCs) have emerged as a next-generation therapeutic platform, combining the target specificity of peptides with the pharmacological potency of small-molecule drugs. As an evolution beyond antibody–drug conjugates (ADCs), PDCs offer distinct advantages, including enhanced cellular permeability, improved drug selectivity, and versatile design flexibility. This review provides a comprehensive analysis of the fundamental components of PDCs, including homing peptide selection, linker engineering, and payload optimization, alongside strategies to address their inherent challenges, such as stability, bioactivity, and clinical translation barriers. Therapeutic applications of PDCs span oncology, infectious diseases, metabolic disorders, and emerging areas like COVID-19, with several conjugates advancing in clinical trials and achieving regulatory milestones. Innovations, including bicyclic peptides, supramolecular architectures, and novel linker technologies, are explored as promising avenues to enhance PDC design. Additionally, this review examines the clinical trajectory of PDCs, emphasizing their therapeutic potential and highlighting ongoing trials that exemplify their efficacy. By addressing limitations and leveraging emerging advancements, PDCs hold immense promise as targeted therapeutics capable of addressing complex disease states and driving progress in precision medicine.
AB - Peptide–drug conjugates (PDCs) have emerged as a next-generation therapeutic platform, combining the target specificity of peptides with the pharmacological potency of small-molecule drugs. As an evolution beyond antibody–drug conjugates (ADCs), PDCs offer distinct advantages, including enhanced cellular permeability, improved drug selectivity, and versatile design flexibility. This review provides a comprehensive analysis of the fundamental components of PDCs, including homing peptide selection, linker engineering, and payload optimization, alongside strategies to address their inherent challenges, such as stability, bioactivity, and clinical translation barriers. Therapeutic applications of PDCs span oncology, infectious diseases, metabolic disorders, and emerging areas like COVID-19, with several conjugates advancing in clinical trials and achieving regulatory milestones. Innovations, including bicyclic peptides, supramolecular architectures, and novel linker technologies, are explored as promising avenues to enhance PDC design. Additionally, this review examines the clinical trajectory of PDCs, emphasizing their therapeutic potential and highlighting ongoing trials that exemplify their efficacy. By addressing limitations and leveraging emerging advancements, PDCs hold immense promise as targeted therapeutics capable of addressing complex disease states and driving progress in precision medicine.
KW - linkers
KW - peptide
KW - peptide–drug conjugates
KW - stability
KW - targeted therapeutics
KW - theranostic
UR - https://www.scopus.com/pages/publications/105006771302
U2 - 10.3390/bioengineering12050481
DO - 10.3390/bioengineering12050481
M3 - Review article
AN - SCOPUS:105006771302
SN - 2306-5354
VL - 12
JO - Bioengineering
JF - Bioengineering
IS - 5
M1 - 481
ER -