Journal ArticleDOI
The Future of Peptide‐based Drugs
TLDR
The suite of currently used drugs can be divided into two categories - traditional'small molecule' drugs with typical molecular weights of 5000 Da that are not orally bioavailable and need to be delivered via injection as mentioned in this paper.Abstract:
The suite of currently used drugs can be divided into two categories - traditional 'small molecule' drugs with typical molecular weights of 5000 Da that are not orally bioavailable and need to be delivered via injection. Due to their small size, conventional small molecule drugs may suffer from reduced target selectivity that often ultimately manifests in human side-effects, whereas protein therapeutics tend to be exquisitely specific for their targets due to many more interactions with them, but this comes at a cost of low bioavailability, poor membrane permeability, and metabolic instability. The time has now come to reinvestigate new drug leads that fit between these two molecular weight extremes, with the goal of combining advantages of small molecules (cost, conformational restriction, membrane permeability, metabolic stability, oral bioavailability) with those of proteins (natural components, target specificity, high potency). This article uses selected examples of peptides to highlight the importance of peptide drugs, some potential new opportunities for their exploitation, and some difficult challenges ahead in this field.read more
Citations
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Coronavirus envelope protein: current knowledge
TL;DR: Data shows that E is involved in critical aspects of the viral life cycle and that CoVs lacking E make promising vaccine candidates, which can aid in the production of effective anti-coronaviral agents for both human CoVs and enzootic CoVs.
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Small molecules, big targets: drug discovery faces the protein–protein interaction challenge
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Journal ArticleDOI
The Current State of Peptide Drug Discovery: Back to the Future?
TL;DR: An emphasis is placed on describing research efforts to overcome the inherent weaknesses of peptide drugs, in particular their poor pharmacokinetic properties, and how these efforts have been critical to the discovery, design, and subsequent development of novel therapeutics.
Journal ArticleDOI
Advances in targeting cyclic nucleotide phosphodiesterases
Donald H. Maurice,Hengming Ke,Faiyaz Ahmad,Yousheng Wang,Jay Young Chung,Vincent C. Manganiello +5 more
TL;DR: Pharmaceutical interest in PDEs has been reignited by the increasing understanding of the roles of individual P DEs in regulating the subcellular compartmentalization of specific cyclic nucleotide signalling pathways, by the structure-based design of novel specific inhibitors and by the development of more sophisticated strategies to target individual PDE variants.
Journal ArticleDOI
Basics and recent advances in peptide and protein drug delivery.
TL;DR: Oral and transdermal peptide drug delivery is discussed, focusing on barriers and solutions to absorption and stability issues, and methods to increase systemic stability and site-specific delivery are also discussed.
References
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Journal ArticleDOI
Molecular properties that influence the oral bioavailability of drug candidates.
Daniel F. Veber,Stephen R. Johnson,Hung-Yuan Cheng,Brian R. Smith,Keith W. Ward,Kenneth D. Kopple +5 more
TL;DR: Reduced molecular flexibility, as measured by the number of rotatable bonds, and low polar surface area or total hydrogen bond count are found to be important predictors of good oral bioavailability, independent of molecular weight.
Journal ArticleDOI
Natural Products as Sources of New Drugs over the Last 25 Years
David J. Newman,Gordon M. Cragg +1 more
TL;DR: This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003 and is able to identify only one de novo combinatorial compound approved as a drug in this 25 plus year time frame.
Journal ArticleDOI
Natural Products As Sources of New Drugs over the 30 Years from 1981 to 2010
David J. Newman,Gordon M. Cragg +1 more
TL;DR: This review is an updated and expanded version of the three prior reviews and adds a new designation, "natural product botanical" or "NB", to cover those botanical "defined mixtures" that have now been recognized as drug entities by the FDA and similar organizations.
Journal ArticleDOI
Drug-like properties and the causes of poor solubility and poor permeability
TL;DR: There are currently about 10000 drug-like compounds, and true diversity does not exist in experimental combinatorial chemistry screening libraries because current ADME experimental screens are multi-mechanisms, and predictions get worse as more data accumulates.
Journal ArticleDOI
Activation of Apoptosis in Vivo by a Hydrocarbon-Stapled BH3 Helix
Loren D. Walensky,Andrew L. Kung,Andrew L. Kung,Iris Escher,Thomas J. Malia,Thomas J. Malia,Scott Barbuto,Renee D. Wright,Gerhard Wagner,Gregory L. Verdine,Stanley J. Korsmeyer +10 more
TL;DR: Hydrocarbon stapling of native peptides may provide a useful strategy for experimental and therapeutic modulation of protein-protein interactions in many signaling pathways.