Opioids, plasticity and phrenic motor performance: investigating the off‐target effects of acute morphine administration

Murchú, Seán C. Ó; Slyne, Aoife D.

doi:10.1113/jp282068

Cited by 2 publications

(2 citation statements)

References 5 publications

(22 reference statements)

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“…Despite the drug-likeness of analgesic compounds, these molecules often display target promiscuity and produce harmful off-target effects. 132 Opioids, such as morphine or fentanyl, are well-known examples of highly potent analgesic compounds with a high potential for abuse and instances of fatal overdose. 133 According to the CDC, opioid overdose was responsible for over 645,000 deaths between 1999 and 2021.…”

Section: Peptide−drug Conjugates For Cns Targets Peptide−drug Conjuga...mentioning

confidence: 99%

“…Medicinal chemists have addressed this issue with the development of highly potent, small-molecule analgesics that typically interact with G protein-coupled receptors (GPCRs) to relieve pain. Despite the drug-likeness of analgesic compounds, these molecules often display target promiscuity and produce harmful off-target effects . Opioids, such as morphine or fentanyl, are well-known examples of highly potent analgesic compounds with a high potential for abuse and instances of fatal overdose .…”

Section: Peptide–drug Conjugates For Cns Targetsmentioning

confidence: 99%

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Peptide–Drug Conjugates: An Emerging Direction for the Next Generation of Peptide Therapeutics

Dean,

Jelú-Reyes,

Allen

et al. 2024

J. Med. Chem.

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Building on recent advances in peptide science, medicinal chemists have developed a hybrid class of bioconjugates, called peptide−drug conjugates, that demonstrate improved efficacy compared to peptides and small molecules independently. In this Perspective, we discuss how the conjugation of synergistic peptides and small molecules can be used to overcome complex disease states and resistance mechanisms that have eluded contemporary therapies because of their multi-component activity. We highlight how peptide−drug conjugates display a multi-factor therapeutic mechanism similar to that of antibody−drug conjugates but also demonstrate improved therapeutic properties such as less-severe off-target effects and conjugation strategies with greater site-specificity. The many considerations that go into peptide−drug conjugate design and optimization, such as peptide/smallmolecule pairing and chemo-selective chemistries, are discussed. We also examine several peptide−drug conjugate series that demonstrate notable activity toward complex disease states such as neurodegenerative disorders and inflammation, as well as viral and bacterial targets with established resistance mechanisms. ■ SIGNIFICANCE• Juxtaposition of peptide−drug conjugates and antibody−drug conjugates with a focus on challenges that can be overcome with peptide−drug conjugate strategies. • Considerations for the design and optimization of peptide−drug conjugates. • Analysis of several peptide−drug conjugate series that demonstrate effectiveness toward drug-resistant infections and complex disease states.

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Section: Peptide−drug Conjugates For Cns Targets Peptide−drug Conjuga...mentioning

confidence: 99%

Section: Peptide–drug Conjugates For Cns Targetsmentioning

confidence: 99%

Peptide–Drug Conjugates: An Emerging Direction for the Next Generation of Peptide Therapeutics

Dean,

Jelú-Reyes,

Allen

et al. 2024

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

Insufficient autophagy enables the nuclear factor erythroid 2-related factor 2 (NRF2) to promote ferroptosis in morphine-treated SH-SY5Y cells

Huang,

Yan,

Chen

et al. 2023

Psychopharmacology

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Opioids, plasticity and phrenic motor performance: investigating the off‐target effects of acute morphine administration

Cited by 2 publications

References 5 publications

Peptide–Drug Conjugates: An Emerging Direction for the Next Generation of Peptide Therapeutics

Peptide–Drug Conjugates: An Emerging Direction for the Next Generation of Peptide Therapeutics

Insufficient autophagy enables the nuclear factor erythroid 2-related factor 2 (NRF2) to promote ferroptosis in morphine-treated SH-SY5Y cells

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