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

  1. 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.
  2. The developed peptide drugs often use endogenous peptides as templates, which usually have a higher target affinity and a smaller risk of off-target.
  3. 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.
  4. 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.
  5. 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.
  6. Peptide drugs may develop immunogenicity as the number of amino acids increases.
Drug Small-molecules Peptides Proteins
Molecular Weight < 500 500-10000 >10000
Stability Better Good Bad
Activity Low High High
Specificity Weak Strong Strong
Immunogenicity No No or Low Yes
Purity High High Low
Cost Low High Higher

Table 1 Comparison of peptide with small-molecule and protein

Marketed Peptide Drugs

Type Name Length Company
Adrenocorticotropic hormone (ACTH) and its derivatives

 

Corticorelin 41aa Ferring Pharm
Cosyntropin 24aa Celtic Pharma
Seractide 39aa Armour Pharm
Cholecystokinin analogs Ceruletide 10aa Pharmacia and Upjohn, Farmitalia Carlo Erba
Sincalide 8aa Bracco Diagnostics
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,

Kabi,Pharmacia

Somatorelin 44aa Ferring Pharm
Tesamorelin 44aa Theratechnologies
Secretin Secretin (human) 27aa ChiRhoClin
Secretin (porcine) 27aa ChiRhoClin
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
Elcatonin 31aa Gelacs Innovation
Human Calcitonin 32aa Novartis Pharma
Parathyroid hormone derivatives Teriparatide 34aa Eli Lilly
Oxytocin analogs and antagonists Atosiban 9aa Ferring Pharms
Carbetocin 8aa 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
Goserelin 10aa AstraZeneca
Histrelin 9aa Endo Pharms, Roberts Pharma, Shire
Leuprolide 9aa Abbott, Alza, AstellasPharma, Bayer, Bedford Labs, Genzyme, Johnson&Johnson, QLT, Sanofi-Aventis, Takeda,Teva, Wyeth
Nafarelin 10aa Pfizer, Searle
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
Ganirelix 10aa Organon
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
Somatostatin 14aa Merck-Serono
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
Lypressin 9aa Sandoz-Novartis Pharma
Phenypressin 9aa Globopharm
Terlipressin 12aa Ferring Pharms
Anti-HIV drugs Enfuvirtide 36aa Roche
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
Angiotensin Icatibant 10aa Jerini AG
Diabetes Exenatide 39aa Amylin Pharms, Eli Lilly
Liraglutide 31aa Novo Nordisk
Lixisenatide 44aa Sanofi-Aventis
Albiglutide 30aa GSK
Dulaglutide 46aa Eli Lilly
Pramlintide 37aa Amylin Pharms
Others Linasclotide cyclic peptide Ironwood Pharmaceuticals/Forest Laboratories, Almirall
Sinaspultide 21aa Discovery Labs
Pasireotide cyclic peptide Novartis
Teduglutide 33aa NPS Pharms, Nycomed
Peginesatide 42aa Affymax,takeda
Pentagastrin 5aa Cambridge Labs, SERB Labs, Wyeth-Ayerst Labs
Aviptadil 28aa Senatalk

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.