The Induction of Prolonged Myelopoietic Effects in Monkeys by GW003, A Recombinant Human Granulocyte Colony-Stimulating Factor Genetically Fused to Recombinant Human Albumin

Xu, Xianxing; Yang, Jingwen; Liu, Yunlong; Shan, Chengqi; Wang, Qiushi; Chen, Zhihang; Cheng, Yiwei

doi:10.1002/jps.24121

Cited by 6 publications

(4 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it has a short in vivo half-life, resulting in frequent injection and low patient compliance ( Akizawa et al, 1995 ). To overcome these problems, the long-acting technologies such as polyethylene glycol modification (PEGylation) ( Wu et al, 2015 ), protein fusion ( Xu et al, 2015 ; Do et al, 2017 ), and new dosage forms technologies ( Kim and Park, 2004 ) have been used for the development of long-acting rhG-CSF. Among these technologies, PEGylation is one of the most successful methods, and several PEGylation rhG-CSF products (e.g., Pegfilgrastim ( Piedmonte and Treuheit, 2008 )) have been approved for clinical use.…”

Section: Introductionmentioning

confidence: 99%

Preparation and Characterization of Site-Specific Fatty Chain-Modified Recombinant Human Granulocyte Colony Stimulating Factor

Wang

Liu

et al. 2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

The clinical use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) is limited by its short serum half-life. In this study, a long-acting strategy for site-specific modification of rhG-CSF with 1-pentadecyl-1H-pyrrole-2,5-dione (C15 fatty chain-maleimide, C15-MAL) was studied in mixed DMSO-aqueous solutions. The factors influencing the conjugation reaction were investigated and optimized, and a high yield of the desired product (C15-rhG-CSF) was achieved. Subsequently, C15-rhG-CSF product was efficiently purified using preparative liquid chromatography, and further characterized. Circular dichroism spectroscopy analysis showed that the secondary structure of C15-rhG-CSF had no significant difference from unmodified rhG-CSF. C15-rhG-CSF retained 87.2% of in vitro bioactivity of unmodified rhG-CSF. The pharmacokinetic study showed that the serum half-life of C15-rhG-CSF in mice was 2.08-fold longer than that of unmodified rhG-CSF. Furthermore, C15-rhG-CSF by single-dose subcutaneous administration showed better in vivo efficacy than those of both PEG10k-rhG-CSF by single-dose administration and rhG-CSF by multiple doses administration. This study demonstrated the potential of C15-rhG-CSF being developed into a novel drug candidate as well as an efficient process for the development of long-acting protein and peptide drugs.

show abstract

Section: Introductionmentioning

confidence: 99%

Preparation and Characterization of Site-Specific Fatty Chain-Modified Recombinant Human Granulocyte Colony Stimulating Factor

Wang

Liu

et al. 2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

show abstract

“…They do not affect the recovery of the B-lymphocytic cell populations. Myelopeptides are a mixture of peptides and often cause a hyperthermic reaction, dizziness, and severe allergic reactions up to anaphylactic shock, nausea, vomiting, edema, sleep disturbance, and anorexia [ 5 , 8 , 9 , 10 , 11 , 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…They stimulate the production of PGE 2 by malignant cells, which leads to pericancrotic inflammation [ 7 ] and suppression of antitumor immunity. Cytokine-based preparations contain cytokines, interferons, and colony-stimulating factors [ 8 ] (filgrastim, lenograstim, pegfilgrastim, empegfilgrastim, roncoleukin) that stimulate interferogenesis, T- and B-lymphopoiesis [ 9 ], and immune responses, and participate in angiogenesis, apoptosis, chemo taxis, and embryogenesis [ 10 , 11 ]. However cytokine drugs can cause uncontrolled immune reactions [ 12 ], septic shock, decreased contractility of the myocardium and smooth muscle cells of blood vessels [ 13 ], induce “bone” pain, increase permeability of the endothelium, and impair microcirculation in organs, decrease blood pressure [ 14 ], and cause hypoglycemia [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Stimulation of B-Lymphopoiesis by Administration of a Trimecaine-Based Ionic Compound in Cyclophosphamide-Induced Hematopoietic-Depressive Model

et al. 2023

View full text Add to dashboard Cite

According to the WHO, the secondary form of hematopoietic-depressive status increases the risk of death in people with oncological, infectious, and hormonal diseases. The choice of drugs that stimulate the hematopoietic activity of B-lymphopoiesis is limited. The current leucopoiesis drugs have a number of side effects: thymic preparations stimulate the production of PGE2, which causes chronic inflammation and various autoimmune diseases through the differentiation of T helper 1 (Th1) cells, the proliferation of Th17 cells, and the production of IL-22 from Th22 cells through EP2 and EP4 receptors; cytokine preparations can cause uncontrolled immune reactions and impaired contractility of smooth and cardiac muscles; drugs based on nucleic acids can stimulate the division of all cells, including bacterial and cancerous ones. The use of oligonucleotides such as ribozymes and antisense oligodeoxynucleotides (AS-ODNs) shows promise as therapeutic moieties, but faces a number of challenges such as nuclease sensitivity, off-target effects, and efficient delivery. The search for substances that stimulate B-lymphopoiesis among ionic compounds was motivated by the discovery of the unique properties of lidocaine docusate, one of the first ionic liquid forms of the known drugs. The lidocaine docusate (protonated form of lidocaine (2-(diethylamino)-N-(2,6-dimethylphenyl) acetamide + docusate-anion (dioctylsulfosuccinate))) suppresses the division of pheochromocytoma cells and activates immunity in rats. The trimecaine-based ionic compound (TIC) demonstrates high B-lymphopoiesis-stimulating activity. The TIC compound stimulates an increase in the volume of transitional B cells, which play an important role for further differentiation and formation of a sufficient number of mature B1 cells and mature B2 cells, where mature B2 cells make up the bulk of the functional population of B lymphocytes. The TIC compound most strongly stimulated the restoration of the number of marginal zone B cells, follicular B cells, and activated germinal center B cells after the cytotoxic emptying of the follicular centers of the spleen induced cyclophosphamide. It significantly exceeds the activity of the comparison drug methyluracil. The TIC compound does not affect the level of pro-B, pre-B-I, or pre-B-II bone marrow cells, which prevents the risk of the formation of immature functionally defective cells.

show abstract

“…Today immunostimulants of microbial, thymic, bone marrow, cytokine, nucleic, animal, plant and synthetic origin are known. On the pharmaceutical market of the Republic of Kazakhstan, immunostimulants of domestic production are represented only by biologically active supplements that are not pharmaceuticals [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Biological activity of 4-ethynyl-, 4-oxy-, 4-butoxypropylpyperidine and azaheterocyclic compounds

Daulet

Baktybayeva

Sokolenko

et al. 2021

IJBCh

View full text Add to dashboard Cite

The immune system of humans and higher animals performs an important function of maintaining the constancy of the internal environment of the body by detecting and eliminating foreign substances of an antigenic nature, both endogenously created and exogenously penetrating. This function of the immune system is performed by factors of innate and acquired immunity. As the name suggests, immunostimulants are the agents boosting the immune response. The new chemical series of compounds is promising for the search new effective immunostimulating drugs. Acute toxicity and the effect on peripheral blood hemogram parameters and on the subpopulation composition of lymphocytes were determined in the compounds (piperidine-containing derivatives):ethoxyethyl)-4-ethynyl-4hydroxypiperidine) dihydrochloride and, 1:1 complexes of β-cyclodextrin with 1-(2-ethoxyethyl)-4-(2-ethoxyethoxyl)-4-ethynylpiperidine, 1-(2-ethoxyethyl)-4-(2-methoxyethoxyl)-4-ethynylpiperidine, 7-(2-methoxyethyl)-2,2-dimethyl-3-thia-7-azabicyclo[3.3.1]nonane or 3-(2-morpholinoethyl)-7-(3isopropoxypropyl) diazabicyclo[3.3.1] nonane with β-cyclodextrin. Compound ˗ 1-(3-n-butoxypropyl) piperidine-3-methyl-4-spiro-5'-imidazolidine-2',4'-dione, exceeds the immunostimulating activity of the comparison drug of levamizole by 3.1 times and shows low toxicity.

show abstract

The Induction of Prolonged Myelopoietic Effects in Monkeys by GW003, A Recombinant Human Granulocyte Colony-Stimulating Factor Genetically Fused to Recombinant Human Albumin

Cited by 6 publications

References 29 publications

Preparation and Characterization of Site-Specific Fatty Chain-Modified Recombinant Human Granulocyte Colony Stimulating Factor

Preparation and Characterization of Site-Specific Fatty Chain-Modified Recombinant Human Granulocyte Colony Stimulating Factor

Stimulation of B-Lymphopoiesis by Administration of a Trimecaine-Based Ionic Compound in Cyclophosphamide-Induced Hematopoietic-Depressive Model

Biological activity of 4-ethynyl-, 4-oxy-, 4-butoxypropylpyperidine and azaheterocyclic compounds

Contact Info

Product

Resources

About