|
|
Pharmacy Information 2026
多肽类药物研发现状
|
Abstract:
近年来，多肽药物研究取得了显著的进展，越来越多的多肽药物被开发并应用于临床。多肽药物在肿瘤、抗菌、心血管系统疾病、糖尿病等疾病的预防、诊断和治疗中得到了广泛应用，并展现出广阔的发展前景。本文旨在简要介绍多肽药物的来源、特点以及先导多肽的发现，并着重综述在不同疾病治疗领域国内外多肽药物的研发概况。新型多肽药物如多功能肽、多肽偶联药物、多肽疫苗等的出现，极大地推动了多肽药物领域的繁荣发展。本文还讨论了多肽药物未来发展和挑战，以期为该类新药的研发提供参考。
Peptide drugs have become a prominent area of research with numerous advancements contributing to their increased development and application in clinical practice. These drugs are now widely utilized in the prevention, diagnosis and treatment of various diseases, including cancer, bacterial infections, cardiovascular disorders, and diabetes. The trend of peptide drug has shown great promise and continues to expand. This article provides a brief introduction to the origins, characteristics and discovery of lead peptides in the research. This article also focuses on summarizing the research and development of peptide drugs in different disease treatment fields. The emergence of novel peptide drugs, such as multifunctional peptides, peptide-drug conjugates, and peptide vaccines, has greatly propelled the prosperity and development of the peptide-based therapeutics field. Additionally, the article discusses the future development prospects and challenges that peptide drugs may encounter which aims to provide valuable references involved in the exploration of new peptide drugs for researchers and developers.
| [1] | Wang, L., Wang, N., Zhang, W., Cheng, X., Yan, Z., Shao, G., et al. (2022) Therapeutic Peptides: Current Applications and Future Directions. Signal Transduction and Targeted Therapy, 7, Article No. 48. https://doi.org/10.1038/s41392-022-00904-4 |
| [2] | Muttenthaler, M., King, G.F., Adams, D.J. and Alewood, P.F. (2021) Trends in Peptide Drug Discovery. Nature Reviews Drug Discovery, 20, 309-325. https://doi.org/10.1038/s41573-020-00135-8 |
| [3] | Xiao, W., Jiang, W., Chen, Z., Huang, Y., Mao, J., Zheng, W., et al. (2025) Advance in Peptide-Based Drug Development: Delivery Platforms, Therapeutics and Vaccines. Signal Transduction and Targeted Therapy, 10, Article No. 74. https://doi.org/10.1038/s41392-024-02107-5 |
| [4] | Lau, J.L. and Dunn, M.K. (2018) Therapeutic Peptides: Historical Perspectives, Current Development Trends, and Future Directions. Bioorganic & Medicinal Chemistry, 26, 2700-2707. https://doi.org/10.1016/j.bmc.2017.06.052 |
| [5] | Ghosh, D., Peng, X., Leal, J. and Mohanty, R.P. (2017) Peptides as Drug Delivery Vehicles across Biological Barriers. Journal of Pharmaceutical Investigation, 48, 89-111. https://doi.org/10.1007/s40005-017-0374-0 |
| [6] | Góngora-Benítez, M., Tulla-Puche, J. and Albericio, F. (2013) Multifaceted Roles of Disulfide Bonds. Peptides as Therapeutics. Chemical Reviews, 114, 901-926. https://doi.org/10.1021/cr400031z |
| [7] | Davda, J., Declerck, P., Hu-Lieskovan, S., Hickling, T.P., Jacobs, I.A., Chou, J., et al. (2019) Immunogenicity of Immunomodulatory, Antibody-Based, Oncology Therapeutics. Journal for ImmunoTherapy of Cancer, 7, Article 105. https://doi.org/10.1186/s40425-019-0586-0 |
| [8] | Craik, D.J., Fairlie, D.P., Liras, S. and Price, D. (2012) The Future of Peptide-Based Drugs. Chemical Biology & Drug Design, 81, 136-147. https://doi.org/10.1111/cbdd.12055 |
| [9] | López-Otín, C. and Bond, J.S. (2008) Proteases: Multifunctional Enzymes in Life and Disease. Journal of Biological Chemistry, 283, 30433-30437. https://doi.org/10.1074/jbc.r800035200 |
| [10] | Alavi, S.E., Cabot, P.J. and Moyle, P.M. (2019) Glucagon-Like Peptide-1 Receptor Agonists and Strategies to Improve Their Efficiency. Molecular Pharmaceutics, 16, 2278-2295. https://doi.org/10.1021/acs.molpharmaceut.9b00308 |
| [11] | Merseburger, A.S. and Roesch, M.C. (2022) Advanced Delivery of Leuprorelin Acetate for the Treatment of Prostatic Cancer. Expert Review of Anticancer Therapy, 22, 703-715. https://doi.org/10.1080/14737140.2022.2082947 |
| [12] | Han, L., Zhai, C., Da, L. and Sun, Y. (2025) The Effect of Leuprolide Acetate 11.25 mg 3-Month Formulation in Children with Central Precocious Puberty: A Systematic Review and Meta-Analysis. Advances in Therapy, 42, 5282-5299. https://doi.org/10.1007/s12325-025-03222-7 |
| [13] | Zhang, P., Jiang, Y., Xu, C., Zhou, L., Zheng, H., Xie, D., et al. (2023) Pegmolesatide for the Treatment of Anemia in Patients Undergoing Dialysis: A Randomized Clinical Trial. eClinicalMedicine, 65, Article ID: 102273. https://doi.org/10.1016/j.eclinm.2023.102273 |
| [14] | Toivanen, P.I., Nieminen, T., Laakkonen, J.P., Heikura, T., Kaikkonen, M.U. and Ylä-Herttuala, S. (2017) Snake Venom VEGF Vammin Induces a Highly Efficient Angiogenic Response in Skeletal Muscle via VEGFR-2/NRP Specific Signaling. Scientific Reports, 7, Article No. 5525. https://doi.org/10.1038/s41598-017-05876-y |
| [15] | Ma, C., Wei, T., Hua, Y., Wang, Z. and Zhang, L. (2021) Effective Antitumor of Orally Intestinal Targeting Penetrating Peptide-Loaded Tyroserleutide/PLGA Nanoparticles in Hepatocellular Carcinoma. International Journal of Nanomedicine, 16, 4495-4513. https://doi.org/10.2147/ijn.s315713 |
| [16] | Awan, A.R., Shaw, W.M. and Ellis, T. (2016) Biosynthesis of Therapeutic Natural Products Using Synthetic Biology. Advanced Drug Delivery Reviews, 105, 96-106. https://doi.org/10.1016/j.addr.2016.04.010 |
| [17] | George, C., Byun, A. and Howard-Thompson, A. (2018) New Injectable Agents for the Treatment of Type 2 Diabetes Part 2—Glucagon-Like Peptide-1 (GLP-1) Agonists. The American Journal of Medicine, 131, 1304-1306. https://doi.org/10.1016/j.amjmed.2018.05.043 |
| [18] | Hauser, A.S., Attwood, M.M., Rask-Andersen, M., Schiöth, H.B. and Gloriam, D.E. (2017) Trends in GPCR Drug Discovery: New Agents, Targets and Indications. Nature Reviews Drug Discovery, 16, 829-842. https://doi.org/10.1038/nrd.2017.178 |
| [19] | Hamad, F., Elnour, A.A., Elamin, A., Mohamed, S., Yousif, I., Don, J., et al. (2021) Systematic Review of Glucagon-Like Peptide One Receptor Agonist Liraglutide of Subjects with Heart Failure with Reduced Left Ventricular Ejection Fraction. Current Diabetes Reviews, 17, 280-292. https://doi.org/10.2174/1573399816999200821164129 |
| [20] | Knudsen, L.B. and Lau, J. (2019) The Discovery and Development of Liraglutide and Semaglutide. Frontiers in Endocrinology, 10, Article 155. https://doi.org/10.3389/fendo.2019.00155 |
| [21] | Li, Y., Cheng, Z., Lu, W., Li, P., Jiang, H., Yang, J., et al. (2023) Efficacy of Noiiglutide Injection on Body Weight in Obese Chinese Adults without Diabetes: A Multicentre, Randomized, Double‐Blind, Placebo‐Controlled, Phase 2 Trial. Diabetes, Obesity and Metabolism, 26, 1057-1068. https://doi.org/10.1111/dom.15407 |
| [22] | Jayaweera, S.P.E., Wanigasinghe Kanakanamge, S.P., Rajalingam, D. and Silva, G.N. (2021) Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma. Frontiers in Oncology, 11, Article 740796. https://doi.org/10.3389/fonc.2021.740796 |
| [23] | Gomes, N.G.M., Valentao, P., Andrade, P.B., and Pereira, R.B., (2020) Plitidepsin to Treat Multiple Myeloma. Drugs of Today, 56, 337-347. https://doi.org/10.1358/dot.2020.56.5.3135886 |
| [24] | Li, C.M., Haratipour, P., Lingeman, R.G., Perry, J.J.P., Gu, L., Hickey, R.J., et al. (2021) Novel Peptide Therapeutic Approaches for Cancer Treatment. Cells, 10, Article 2908. https://doi.org/10.3390/cells10112908 |
| [25] | Desgrosellier, J.S. and Cheresh, D.A. (2010) Integrins in Cancer: Biological Implications and Therapeutic Opportunities. Nature Reviews Cancer, 10, 9-22. https://doi.org/10.1038/nrc2748 |
| [26] | Alves de Souza, S.M., Hernández-Ledesma, B. and de Souza, T.L.F. (2022) Lunasin as a Promising Plant-Derived Peptide for Cancer Therapy. International Journal of Molecular Sciences, 23, Article 9548. https://doi.org/10.3390/ijms23179548 |
| [27] | Yang, Y. (2015) Cancer Immunotherapy: Harnessing the Immune System to Battle Cancer. Journal of Clinical Investigation, 125, 3335-3337. https://doi.org/10.1172/jci83871 |
| [28] | Sasikumar, P.G., Ramachandra, R.K., Adurthi, S., Dhudashiya, A.A., Vadlamani, S., Vemula, K., et al. (2019) A Rationally Designed Peptide Antagonist of the PD-1 Signaling Pathway as an Immunomodulatory Agent for Cancer Therapy. Molecular Cancer Therapeutics, 18, 1081-1091. https://doi.org/10.1158/1535-7163.mct-18-0737 |
| [29] | Maxwell, J.E. and Howe, J.R. (2015) Imaging in Neuroendocrine Tumors: An Update for the Clinician. International Journal of Endocrine Oncology, 2, 159-168. https://doi.org/10.2217/ije.14.40 |
| [30] | Zhang, J., Hu, H., Liang, S., Yin, J., Hui, X., Hu, S., et al. (2013) Targeted Radiotherapy with Tumor Vascular Homing Trimeric GEBP11 Peptide Evaluated by Multimodality Imaging for Gastric Cancer. Journal of Controlled Release, 172, 322-329. https://doi.org/10.1016/j.jconrel.2013.08.033 |
| [31] | Escala Cornejo, R.A., García-Talavera, P., Navarro Martin, M., Pérez López, B., García Muñoz, M., Tamayo Alonso, M.P., et al. (2018) Large Cell Neuroendocrine Carcinoma of the Lung with Atypical Evolution and a Remarkable Response to Lutetium Lu 177 Dotatate. Annals of Nuclear Medicine, 32, 568-572. https://doi.org/10.1007/s12149-018-1276-6 |
| [32] | Zhang, M. and Xu, H. (2023) Peptide-Assembled Nanoparticles Targeting Tumor Cells and Tumor Microenvironment for Cancer Therapy. Frontiers in Chemistry, 11, Article 1115495. https://doi.org/10.3389/fchem.2023.1115495 |
| [33] | Rossino, G., Marchese, E., Galli, G., Verde, F., Finizio, M., Serra, M., et al. (2023) Peptides as Therapeutic Agents: Challenges and Opportunities in the Green Transition Era. Molecules, 28, Article 7165. https://doi.org/10.3390/molecules28207165 |
| [34] | Rosenthal, S., Decano, A.G., Bandali, A., et al. (2018) Oritavancin (Orbactiv): A New-Generation Lipoglycopeptide for the Treatment of Acute Bacterial Skin and Skin Structure Infections. P T, 43, 143-179. |
| [35] | Ongey, E.L. and Neubauer, P. (2016) Lanthipeptides: Chemical Synthesis versus in Vivo Biosynthesis as Tools for Pharmaceutical Production. Microbial Cell Factories, 15, Article No. 97. https://doi.org/10.1186/s12934-016-0502-y |
| [36] | Mandel, S., Michaeli, J., Nur, N., Erbetti, I., Zazoun, J., Ferrari, L., et al. (2021) OMN6 a Novel Bioengineered Peptide for the Treatment of Multidrug Resistant Gram Negative Bacteria. Scientific Reports, 11, Article No. 6603. https://doi.org/10.1038/s41598-021-86155-9 |
| [37] | Dumville, J.C., Lipsky, B.A., Hoey, C., Cruciani, M., Fiscon, M. and Xia, J. (2017) Topical Antimicrobial Agents for Treating Foot Ulcers in People with Diabetes. Cochrane Database of Systematic Reviews, 6, CD011038. https://doi.org/10.1002/14651858.cd011038.pub2 |
| [38] | Samreen, Ahmad, I., Malak, H.A. and Abulreesh, H.H. (2021) Environmental Antimicrobial Resistance and Its Drivers: A Potential Threat to Public Health. Journal of Global Antimicrobial Resistance, 27, 101-111. https://doi.org/10.1016/j.jgar.2021.08.001 |
| [39] | de Castro, N., Braun, J., Charreau, I., Lafeuillade, A., Viard, J., Allavena, C., et al. (2016) Incidence and Risk Factors for Liver Enzymes Elevations in Highly Treatment-Experienced Patients Switching from Enfuvirtide to Raltegravir: A Sub-Study of the ANRS-138 EASIER Trial. AIDS Research and Therapy, 13, Article No. 17. https://doi.org/10.1186/s12981-016-0101-3 |
| [40] | Garnock-Jones, K.P. (2012) Boceprevir: A Review of Its Use in the Management of Chronic Hepatitis C Genotype 1 Infection. Drugs, 72, 2431-2456. https://doi.org/10.2165/11209560-000000000-00000 |
| [41] | Youssef, J.G., Lavin, P., Schoenfeld, D.A., Lee, R.A., Lenhardt, R., Park, D.J., et al. (2022) The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients with Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial. Critical Care Medicine, 50, 1545-1554. https://doi.org/10.1097/ccm.0000000000005660 |
| [42] | Bai, Y., Jones, J.C., Wong, S. and Zanin, M. (2021) Antivirals Targeting the Surface Glycoproteins of Influenza Virus: Mechanisms of Action and Resistance. Viruses, 13, Article 624. https://doi.org/10.3390/v13040624 |
| [43] | Yu, D., Ding, X., Liu, Z., Wu, X., Zhu, Y., Wei, H., et al. (2018) Molecular Mechanism of HIV-1 Resistance to Sifuvirtide, a Clinical Trial-Approved Membrane Fusion Inhibitor. Journal of Biological Chemistry, 293, 12703-12718. https://doi.org/10.1074/jbc.ra118.003538 |
| [44] | Lee, G., Lee, Y., Chang, M., Kang, S.U.K., Ryou, J., Lim, J., et al. (2019) P120 BBT-401 Is a Selective Pellino-1 Protein-Protein Interaction Inhibitor in Clinical Development Targeting a First-In-Class Drug for UC Treatment. Inflammatory Bowel Diseases, 25, S58-S58. https://doi.org/10.1093/ibd/izy393.131 |
| [45] | Liossis, S.N. and Staveri, C. (2021) What’s New in the Treatment of Systemic Lupus Erythematosus. Frontiers in Medicine, 8, Article 655100. https://doi.org/10.3389/fmed.2021.655100 |
| [46] | Drucker, D.J. (2019) The Discovery of GLP-2 and Development of Teduglutide for Short Bowel Syndrome. ACS Pharmacology & Translational Science, 2, 134-142. https://doi.org/10.1021/acsptsci.9b00016 |
| [47] | Gorman, D.M., Lee, J., Payne, C.D., Woodruff, T.M. and Clark, R.J. (2021) Chemical Synthesis and Characterisation of the Complement C5 Inhibitory Peptide Zilucoplan. Amino Acids, 53, 143-147. https://doi.org/10.1007/s00726-020-02921-5 |
| [48] | Min, T. and Bain, S.C. (2020) The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials. Diabetes Therapy, 12, 143-157. https://doi.org/10.1007/s13300-020-00981-0 |
| [49] | Ambery, P., Parker, V.E., Stumvoll, M., Posch, M.G., Heise, T., Plum-Moerschel, L., et al. (2018) MEDI0382, a GLP-1 and Glucagon Receptor Dual Agonist, in Obese or Overweight Patients with Type 2 Diabetes: A Randomised, Controlled, Double-Blind, Ascending Dose and Phase 2a Study. The Lancet, 391, 2607-2618. https://doi.org/10.1016/s0140-6736(18)30726-8 |
| [50] | Lin, L., Ting, S., Yufei, H., Wendong, L., Yubo, F. and Jing, Z. (2020) Epitope-Based Peptide Vaccines Predicted against Novel Coronavirus Disease Caused by SARS-CoV-2. Virus Research, 288, Article ID: 198082. https://doi.org/10.1016/j.virusres.2020.198082 |
| [51] | Bhattacharya, M., Sharma, A.R., Patra, P., Ghosh, P., Sharma, G., Patra, B.C., et al. (2020) Development of Epitope‐based Peptide Vaccine against Novel Coronavirus 2019 (SARS‐COV‐2): Immunoinformatics Approach. Journal of Medical Virology, 92, 618-631. https://doi.org/10.1002/jmv.25736 |
| [52] | Mauriello, A., Cavalluzzo, B., Manolio, C., Ragone, C., Luciano, A., Barbieri, A., et al. (2021) Long-Term Memory T Cells as Preventive Anticancer Immunity Elicited by Tua-Derived Heteroclitic Peptides. Journal of Translational Medicine, 19, Article No. 526. https://doi.org/10.1186/s12967-021-03194-6 |
| [53] | Hu, Z., Leet, D.E., Allesøe, R.L., Oliveira, G., Li, S., Luoma, A.M., et al. (2021) Personal Neoantigen Vaccines Induce Persistent Memory T Cell Responses and Epitope Spreading in Patients with Melanoma. Nature Medicine, 27, 515-525. https://doi.org/10.1038/s41591-020-01206-4 |
| [54] | Iversen, P.L., Kipshidze, N., Kipshidze, N., Dangas, G., Ramacciotti, E., Kakabadze, Z., et al. (2023) A Novel Therapeutic Vaccine Targeting the Soluble TNFα Receptor II to Limit the Progression of Cardiovascular Disease: AtheroVax™. Frontiers in Cardiovascular Medicine, 10, Article 1206541. https://doi.org/10.3389/fcvm.2023.1206541 |
| [55] | Cabri, W., Cantelmi, P., Corbisiero, D., Fantoni, T., Ferrazzano, L., Martelli, G., et al. (2021) Therapeutic Peptides Targeting PPI in Clinical Development: Overview, Mechanism of Action and Perspectives. Frontiers in Molecular Biosciences, 8, Article 697586. https://doi.org/10.3389/fmolb.2021.697586 |
| [56] | Abd-Aziz, N. and Poh, C.L. (2022) Development of Peptide-Based Vaccines for Cancer. Journal of Oncology, 2022, Article ID: 9749363. https://doi.org/10.1155/2022/9749363 |
