Abstract
Toxins and venoms produced by different organisms contain peptides that have evolved to have highly selective and potent pharmacological effects on specific targets for protection and predation. Several toxin-derived peptides have become drugs and are used for the management of diabetes, hypertension, chronic pain, and other medical conditions. Despite the similarity in their composition (amino acids as the building blocks), toxin-derived peptide drugs have very profound differences in their structure and conformation, in their physicochemical properties (that affect solubility, stability, etc.), and subsequently in their pharmacokinetics (the processes of absorption, distribution, metabolism, and elimination following their administration to patients). This review summarizes and critically analyzes the pharmacokinetic properties of toxin-derived peptide drugs: (1) the relationship between the chemical structure, physicochemical properties, and the pharmacokinetics of the specific drugs, (2) the major pharmacokinetic properties and parameters of these drugs, and (3) the major pharmacokinetic variability factors of the individual drugs. The structural properties of toxin-derived peptides affect their pharmacokinetics and pose some limitations on their clinical use. These properties should be taken into account during the development of new toxin-derived peptide drugs, and for the efficient and safe use of the clinically approved drugs from this group in the individual patients.
Highlights
Peptides are an important component of toxins and venoms produced by different organisms.They evolved to have highly selective and potent pharmacological effects on specific targets for protection and predation
They originate from different species and affect very different targets at different locations in the body. This necessitates their administration via different routes, including the most common and convenient oral route, and one of the least convenient and invasive routes of administration—an intrathecal infusion mode
Based on their chemical structure, clinically approved toxin-derived peptide drugs can be classified into peptides or peptide-derived drugs; they can be classified into linear or cyclic compounds, which contain or lack intramolecular disulfide bridges
Summary
Peptides are an important component of toxins and venoms produced by different organisms They evolved to have highly selective and potent pharmacological effects on specific targets for protection and predation. These properties, and advances in the detection, analytics, and synthesis of peptides and their derivatives, make them promising leads for the development of new drugs [1]. Despite the similarity in their composition (amino acids as the building blocks), toxin-derived peptides have very profound differences in their structure and conformation. Part of this “chemical space” can apparently lead to successful drug leads and new drugs. The focus of this review is on the drugs that were approved for clinical use (see Table 1 for the details of the analyzed drugs, including their origin, indication, and innovative drug products), and not on the agents that are evaluated currently in pre-clinical or clinical trials, or have been discontinued
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