Peptides are a class of compounds composed of amino acids connected by peptide bonds, and are commonly found as chemically active substances in living organisms.
According to the classification system commonly used in the international pharmaceutical community, drugs with a number of amino acid molecules greater than 100 belong to protein drugs, while drugs with a number of amino acid molecules less than 100 belong to peptide drugs.
According to public information, peptide drugs have advantages such as strong stability, high selectivity, and low side effects. In clinical applications, peptide drugs mimic the physiological effects of ligands by acting on receptors on the surface of cell membranes, thereby exerting their pharmacological effects.
In addition, peptides are mainly cleared through protein hydrolysis degradation and renal filtration, and the hydrolyzed products are amino acids. Therefore, it is generally not considered whether the metabolites of peptide drugs are toxic and have good safety.
Generally speaking, peptide drugs typically have high target affinity and have a low risk of off target. Moreover, compared to recombinant proteins and monoclonal antibodies, peptide drugs have advantages such as low immunogenicity, convenient preservation, and easy patent protection.
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Novo Nordisk released its 2022 financial report, with sales of its GLP-1 analog company Megglutide reaching $10.882 billion, a sharp increase from 2021. At the same time, Lilly also announced its 2022 performance, with GLP-1 analogues showing similar growth in performance, with sales reaching $7.4 billion. The outstanding performance announcements of two drugs have once again brought peptide drugs into people's sight.
In fact, in recent years, peptide drugs have shown unique advantages in patent medicine and lower side effects compared to small molecule drugs and biological agents, leading the research and development boom of many pharmaceutical companies.
At present, tens of thousands of peptides have been discovered in living organisms, and peptides widely participate in and regulate various functional activities of the human body, such as thyroid hormone, insulin, growth factors, etc., all belong to the category of peptide substances.
Insulin can be said to be the first peptide drug, initially extracted from the pancreas of cows and pigs.
The emergence of recombination technology in the 1980s made it possible to clean produce peptide drugs with larger molecular weights.
As of now, there are approximately 180 types of peptide drugs approved globally, with indications mainly related to endocrine, metabolic, tumor, central nervous system, and other fields. Additionally, multiple drugs are in the Phase III clinical stage.
According to Peptide Research, the global sales of peptide drugs (including insulin) in 2021 were $50.53 billion. According to Frost Sullivan's prediction, the global market size of non insulin peptide drugs is expected to increase from $35.7 billion in 2020 to $62.2 billion in 2025, indicating significant growth potential for the peptide drug market.
Due to the advantages and potential market value of peptides as drugs, the research and development of peptide drugs has been booming in recent years. However, with the deepening of research and development, significant progress has been made in the discovery of target sites, structural modification optimization, and delivery pathways of peptide drugs.
What is the future development direction? Perhaps there is great potential in the future in areas such as cell penetrating peptides, peptide coupled drugs, and formulation optimization.
1. Cell Penetrating Peptide
Cellular transmembrane peptides are a type of peptide composed of usually no more than 30 amino acid residues that can directly penetrate the cell membrane and enter the cell.
They can successfully carry active substances (such as small molecule drugs, siRNAs, nanoparticles, etc.) into cells to exert their effects.
Cell penetrating peptides can effectively promote the transdermal absorption of biological macromolecular drugs, and have significant value in targeted formulations, transdermal delivery formulations, and cosmetics, significantly improving the bioavailability of drugs.
2. Peptide Conjugated Drugs
Fusion of peptides with binding ability with cytotoxic or cytokines, directing them to the lesion site, exerting therapeutic effects while reducing toxic side effects.
Many toxins, cytokines, and others are known to have strong tumor cell toxicity, but they can also damage normal cells.
By fusing peptides that can specifically bind to tumor cells with these active factors, these active factors can be specifically concentrated at the tumor site, greatly reducing the concentration of toxins and cytokines used, and reducing damage to normal cells.
3. Formulation Optimization
Due to the physical and chemical properties of peptides themselves, most of them are injection based, especially intravenous injection or intravenous drip. Improving the delivery method of peptide drugs has become the direction of next-generation peptide drug research and development.
Therefore, in recent years, in addition to classic subcutaneous, muscular, and intravenous administration, other delivery routes have gradually developed, including mucosal delivery (such as nasal, pulmonary, or sublingual), oral delivery, and transdermal delivery.
Among them, nasal administration has developed rapidly. Taking the commercially available nasal delivery peptide drug Miacalcin as an example, its active ingredient is the peptide calcitonin Salmon, which is a calcitonin hormone found in salmon.
Like human calcitonin, salmon calcitonin is a peptide hormone secreted by parafollicular cells in the thyroid gland to respond to hypercalcemia. Miacalcin nasal spray is used to treat osteoporosis in postmenopausal women for at least 5 years. Miacalcin nasal spray is suitable for patients who are not suitable for alternative therapy.
In summary, peptide drugs with a relatively simple research and development process, a success rate twice higher than small molecule drugs, a short average research and development cycle, and a low cost, between the difficulty of discovering and screening small molecules, high technical barriers to the development of large molecule antibody drugs, and research and development difficulties, are one of the highly promising new drug therapies.
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