What is Peptide Drugs?
Peptide is a type of compound formed by connecting multiple amino acids through peptide bonds, usually composed of 10-100 amino acid molecules, and its connection method is the same as that of protein. The relative molecular mass is less than 10,000. In recent years, with the development and maturity of peptide synthesis technology, peptide drugs have become one of the hot spots of drug research and development. Because of their wide indications, high safety, and remarkable efficacy, they have been widely used in the prevention, diagnosis and treatment of tumors, cardiovascular and cerebrovascular, hepatitis, diabetes, AIDS and other diseases.
Characteristics of peptide drugs
- Peptide drugs have high safety and high target affinity. They are mainly eliminated by proteolytic degradation and renal filtration. The products of hydrolysis are amino acids. Therefore, it is generally not considered whether the metabolites of peptide drugs are toxic.
- The developed peptide drugs often use endogenous peptides as templates, which usually have a higher target affinity and a smaller risk of off-target.
- The probability of peptide drugs being approved for marketing through clinical trials is twice higher than that of small-molecule drugs, and the average R&D cycle is 0.7 years shorter. The development of peptide drugs has also extended to many disease fields, including anti-infection, anti-tumor, physiological regulation, pain, heart failure, osteoporosis, diabetes, vaccines, etc.
- Compared with protein, peptide chemical synthesis technology is mature, easy to separate from impurities or by-products, high purity, and easy to introduce unnatural amino acids. However, the quality, purity and yield of recombinant proteins are difficult to guarantee. And the recombinant proteins cannot be introduced with unnatural amino acids and cannot be amidated at the ends. At the same time, the production cycle is long and the cost is high. Peptides are generally lower in cost than protein and antibody drugs, and higher in synthesis cost than most small molecule drugs.
- Peptides are easily degraded, have a short half-life and a high plasma clearance rate. The biggest problem with peptides is that they cannot be taken orally, mainly because they are easily degraded and difficult to cross the intestinal mucosa. In addition, peptides are easily hydrolyzed by proteolytic enzymes in the blood after entering the blood, and have a short plasma half-life and plasma clearance rate, which affects the efficacy of the drug and the choice of the route of administration, and therefore does not produce drug accumulation.
- Peptide drugs may develop immunogenicity as the number of amino acids increases.
|Molecular Weight||< 500||500-10000||>10000|
|Immunogenicity||No||No or Low||Yes|
Table 1 Comparison of peptide with small-molecule and protein
Marketed Peptide Drugs
|Adrenocorticotropic hormone (ACTH) and its derivatives
|Cholecystokinin analogs||Ceruletide||10aa||Pharmacia and Upjohn, Farmitalia Carlo Erba|
|Thyroid Stimulating Hormone Releasing Hormone||Taltirelin||2aa||Tanabe Seiyaku|
|Protirelin||3aa||Abbott, Ferring Pharms|
|Growth hormone releasing hormone (GHRH) and analogs||Sermorelin||29aa||Serono Labs,
|Thymus hormone||Thymalfasin||28aa||SciClone Pharms International|
|Thymopentin||5aa||Recordari, Italofarmaco, Johnson & Johnson|
|Calcitonin||Salmon Calcitonin||32aa||AstraZeneca,GNR Pharma,Lafon,Lisapharma,Pharmy II,Sandoz-NovartisPharma,Sanofi-Aventis,TRBPharma,Zambon France|
|Human Calcitonin||32aa||Novartis Pharma|
|Parathyroid hormone derivatives||Teriparatide||34aa||Eli Lilly|
|Oxytocin analogs and antagonists||Atosiban||9aa||Ferring Pharms|
|Oxytocin||9aa||Abbott, APP Pharms, Baxter Healthcare, JHP Pharms, King Pharmas, Novartis Pharma, Teva|
|Gonadotropin-releasing hormone (GnRH) and analogues||Buserelin||9aa||Sanofi-Aventis|
|Gonadorelin||10aa||Baxter Healthcare, Ferring Pharms, Sanofi-Aventis, Wyeth Pharms|
|Histrelin||9aa||Endo Pharms, Roberts Pharma, Shire|
|Leuprolide||9aa||Abbott, Alza, AstellasPharma, Bayer, Bedford Labs, Genzyme, Johnson&Johnson, QLT, Sanofi-Aventis, Takeda,Teva, Wyeth|
|Triptorelin||10aa||Debiopharm, Ferring Pharms, Beaufour Ipsen Pharma, Watson Labs|
|Gonadotropin releasing hormone (GnRH) antagonist||Abarelix||10aa||Praecis Pharms, Speciality European Pharma|
|Cetrorelix||10aa||AEterna Zentaris, Merck-Serono|
|Degarelix||10aa||Ferring Pharms, Astellas Pharma|
|Somatostatin analogs and antagonists||Depreotide||10aa||Amersham Health, Berlex Labs, CIS bio Intenational, Nycomed Imaging|
|Edotreotide||7aa||Molecular Insight Pharms|
|Lanreotide||8aa||Beaufour Ipsen Pharma, Globopharm, Tercica|
|Octreotide||8aa||Abraxis Pharma, Bedford Labs, Sandoz-Novartis Pharma, Sun Pharma, Teva|
|Pentetreotide||8aa||Mallinckrodt, Bristol-Myers Squibb|
|Vapreotide||8aa||Debiopharm, H3 Pharma|
|Vasopressin analogs||Argipressin||9aa||Monasrch/King Pharms|
|Desmopressin||9aa||Apotex, Bausch & Lomb Pharms, Barr Labs, Behring, Ferring Pharms, Hospira, Pharmaceutique Noroit, Sanofi-Aventis, Teva|
|Central Nervous System||Glatiramer||4aa||Teva|
|Peripheral nervous system||Ziconotide||25aa||Elan Pharms|
|Cardiovascular||Saralasin||8aa||Norwich-Eaton Pharms, Procter & Gamble|
|Bivalirudin||20aa||Nycomed Pharma, The Medicines Company|
|Eptifibatide||7aa||Millennium Pharms, GSK, Schering-Plough|
|Carperitide||28aa||Japan Asubio Pharma|
|Nesiritide||32aa||Johnson & Johnson|
|Diabetes||Exenatide||39aa||Amylin Pharms, Eli Lilly|
|Others||Linasclotide||cyclic peptide||Ironwood Pharmaceuticals/Forest Laboratories, Almirall|
|Teduglutide||33aa||NPS Pharms, Nycomed|
|Pentagastrin||5aa||Cambridge Labs, SERB Labs, Wyeth-Ayerst Labs|
In the future, the number of peptide drugs in the world will continue to increase. There is no shortage of innovations in peptide drugs and they have great potential. In the future, emerging peptide drugs such as antimicrobial peptides, peptide vaccines, peptide carriers, PDC drugs, etc., are still in the clinical research stage and have very good market prospects. Antimicrobial peptides, as new and powerful broad-spectrum antibiotics, are different from previous antibiotics, and have the advantages of improving immunity and not easy to develop drug resistance. Peptide vaccines use certain peptides to have immunogenicity. They are currently on the market in the field of hepatitis treatment, and a new generation of peptide vaccines in the field of Ebola and AIDS are under development.