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This review is devoted to the 100-year history of the investigation of peptide hormones and the creation of drugs on their basis, starting from the insulin discovery and its introduction into a medical practice in 1921. The basic groups of the peptide hormones are discussed: neurohypophyseal hormones, hypothalamic releasing hormones, incretins, insulin, adrenocorticotropic hormone (ACTH), and calcitonin. The first therapeutic agents based on the peptide hormones were created by a traditional approach that involved the isolation of peptides from animal tissues, their purification to individual compounds, determination of their primary structure, their chemical synthesis or their deep purification, and the creation of a pharmaceutical substance. A modern approach to creation of peptide hormone drugs is based on their consideration as ligands of the corresponding cellular receptors and the use of computer modeling, efficient synthesis methods, and high-throughput screening. The combination of these methods enabled the development of analogs which would be more active than the corresponding natural compounds, exhibit other activities in addition to the hormonal regulation, and be resistant to biodegradation. Such therapeutic agents have been designed on the basis of agonistic and antagonistic analogs of somatostatin and luliberin, and have found wide application in hormonal regulation and cancer treatment. Over the past two decades, the glucagon-like peptide (GLP-1) has been intensively investigated as a potential therapeutic agent. In our review, we describe modifications which resulted in the most highly effective long-acting drugs. Now, natural hormones and their analogs are widely present in the pharmaceutical market.
This review is devoted to the 100-year history of the investigation of peptide hormones and the creation of drugs on their basis, starting from the insulin discovery and its introduction into a medical practice in 1921. The basic groups of the peptide hormones are discussed: neurohypophyseal hormones, hypothalamic releasing hormones, incretins, insulin, adrenocorticotropic hormone (ACTH), and calcitonin. The first therapeutic agents based on the peptide hormones were created by a traditional approach that involved the isolation of peptides from animal tissues, their purification to individual compounds, determination of their primary structure, their chemical synthesis or their deep purification, and the creation of a pharmaceutical substance. A modern approach to creation of peptide hormone drugs is based on their consideration as ligands of the corresponding cellular receptors and the use of computer modeling, efficient synthesis methods, and high-throughput screening. The combination of these methods enabled the development of analogs which would be more active than the corresponding natural compounds, exhibit other activities in addition to the hormonal regulation, and be resistant to biodegradation. Such therapeutic agents have been designed on the basis of agonistic and antagonistic analogs of somatostatin and luliberin, and have found wide application in hormonal regulation and cancer treatment. Over the past two decades, the glucagon-like peptide (GLP-1) has been intensively investigated as a potential therapeutic agent. In our review, we describe modifications which resulted in the most highly effective long-acting drugs. Now, natural hormones and their analogs are widely present in the pharmaceutical market.
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