Peptide-drug conjugates: A new paradigm for targeted cancer therapy

Wang, Mo; Liu, Jiawei; Xia, Mingjing; Yin, Libinghan; Zhang, Ling; Liu, Xifu; Cheng, Yu

doi:10.1016/j.ejmech.2023.116119

Cited by 13 publications

(3 citation statements)

References 95 publications

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“…Mándity and coworkers have created a database of PDCs (ConjuPepBD) that encompasses over 1600 conjugates documented in approximately 230 publications [172]. Lutathera and Pepaxto stand as the sole FDA-approved peptide drug conjugates (PDCs) [173]. However, with the discontinuation of Pepaxto, only one approved PDC remains [166].…”

Section: Peptide Drug Conjugates (Pdcs)mentioning

confidence: 99%

Peptide Therapeutics: Unveiling the Potential against Cancer—A Journey through 1989

Al Musaimi

2024

Cancers

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The United States Food and Drug Administration (FDA) has approved a plethora of peptide-based drugs as effective drugs in cancer therapy. Peptides possess high specificity, permeability, target engagement, and a tolerable safety profile. They exhibit selective binding with cell surface receptors and proteins, functioning as agonists or antagonists. They also serve as imaging agents for diagnostic applications or can serve a dual-purpose as both diagnostic and therapeutic (theragnostic) agents. Therefore, they have been exploited in various forms, including linkers, peptide conjugates, and payloads. In this review, the FDA-approved prostate-specific membrane antigen (PSMA) peptide antagonists, peptide receptor radionuclide therapy (PRRT), somatostatin analogs, antibody–drug conjugates (ADCs), gonadotropin-releasing hormone (GnRH) analogs, and other peptide-based anticancer drugs are analyzed in terms of their chemical structures and properties, therapeutic targets and mechanisms of action, development journey, administration routes, and side effects.

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Section: Peptide Drug Conjugates (Pdcs)mentioning

confidence: 99%

Peptide Therapeutics: Unveiling the Potential against Cancer—A Journey through 1989

Al Musaimi

2024

Cancers

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“…The advancements of analytical structural characterization methods also contributed for the growing interest of this class of compounds [51][52][53][54]. Peptides are also interesting models for molecular modifications [55,56] and conjugation with other molecules [57,58] to improved properties and/or for targeted therapy.…”

Section: Generalitiesmentioning

confidence: 99%

Zilucoplan: A Newly Approved Macrocyclic Peptide for Treatment of Anti-Acetylcholine Receptor Positive Myasthenia Gravis

Costa,

Fernandes

2024

DDC

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Zilucoplan is a synthetic macrocyclic peptide approved by the Food and Drug Administration (FDA), in October 2023, for the treatment of generalized myasthenia gravis. It is considered as an orphan drug that causes the inhibition of terminal complement cascade activation with a dual mechanism of action preventing the formation of the membrane attack complex (MAC) and the destruction of the neuromuscular junction. This drug has been demonstrated to be able to treat the generalized myasthenia gravis without significant adverse effects, with good efficacy, safety, and tolerability profile. Zilucoplan is not only innovative and promising in the therapeutics of generalized myasthenia gravis, but it could also be beneficial for the treatment of other diseases as well as a model for synthesis of analogues to improve pharmacological profile.

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“…One of the most effective approaches to target the tumor site is constructing peptide-drug conjugates (PDCs) by coupling antitumor drugs with tumor-homing peptide ligands that have high affinity to the specific receptors overexpressed on tumor cells via a cleavable linker [2,3]. In recent years, peptide ligands have been increasingly used for conjugation with drugs as a kind of "magic bullet" due to their advantages of easier preparation and structural modification, higher tissue permeability, and lower immunogenicity compared with protein ligands such as monoclonal antibodies [4,5].…”

Section: Introductionmentioning

confidence: 99%

New Transferrin Receptor-Targeted Peptide–Doxorubicin Conjugates: Synthesis and In Vitro Antitumor Activity

Yu,

Mao,

Yang

et al. 2024

Molecules

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Poor selectivity to tumor cells is a major drawback in the clinical application of the antitumor drug doxorubicin (DOX). Peptide–drug conjugates (PDCs) constructed by modifying antitumor drugs with peptide ligands that have high affinity to certain overexpressed receptors in tumor cells are increasingly assessed for their possibility of tumor-selective drug delivery. However, peptide ligands composed of natural L-configuration amino acids have the defects of easy enzymatic degradation and insufficient biological stability. In this study, two new PDCs (LT7-SS-DOX and DT7-SS-DOX) were designed and synthesized by conjugating a transferrin receptor (TfR) peptide ligand LT7 (HAIYPRH) and its retro-inverso analog DT7 (hrpyiah), respectively, with DOX via a disulfide bond linker. Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the DT7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to LT7-SS-DOX. In conclusion, the coupling of antitumor drugs with the DT7 peptide ligand can be used as a promising strategy for the further development of stable and efficient PDCs with the potential to facilitate TfR-targeted drug delivery.

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Peptide-drug conjugates: A new paradigm for targeted cancer therapy

Cited by 13 publications

References 95 publications

Peptide Therapeutics: Unveiling the Potential against Cancer—A Journey through 1989

Peptide Therapeutics: Unveiling the Potential against Cancer—A Journey through 1989

Zilucoplan: A Newly Approved Macrocyclic Peptide for Treatment of Anti-Acetylcholine Receptor Positive Myasthenia Gravis

New Transferrin Receptor-Targeted Peptide–Doxorubicin Conjugates: Synthesis and In Vitro Antitumor Activity

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