电邮这篇文章 Specific Activity of Recombinant Modified Human Glucagon-Like Peptide 1
- 作者: Sannikova E.P.1, Bobkova N.V.2, Tatarnikova O.G.2, Yarotskii S.V.1, Askerova E.V.1, Rykalina N.V.1, Yurin V.L.1, Gracheva T.S.1, Klebanov F.A.1, Zalunin I.A.1, Cheperegin S.E.1, Bulushova N.V.1, Kozlov D.G.1
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隶属关系:
- State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center, Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
- Institute of Cell Biophysics, Russian Academy of Sciences
- 期: 卷 55, 编号 7 (2019)
- 页面: 722-732
- 栏目: Producers, Biology, Selection, and Gene Engineering
- URL: https://journals.rcsi.science/0003-6838/article/view/153089
- DOI: https://doi.org/10.1134/S0003683819070068
- ID: 153089
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详细
An1 original drug, Glypin, has been developed for the treatment of type-II human diabetes mellitus. Its active pharmaceutical substance is a completely biosynthetic, recombinant, modified, human glucagon-like peptide (rmGlp-1) obtained via culturing of E. coli cells. In addition to the GLP-1 portion, which contains the well-known Ala8Gly substitution, the rmGLP-1 protein has an additional amino acid sequence at the C-terminus that includes the heparin-binding peptide of human HB-EGF. Preclinical testing of Glypin specific activity (with Lixumia as a reference drug) was performed. A commercial preparation of Lixumia served as the main reference drug for comparison with the specific activity of Glypin. During preclinical studies of both medicines, it was shown that Glypin and Lixumia have similar mechanisms, power, and time of action upon subcutaneous and intramuscular introductions, as well as comparable therapeutic effects under long-term use. Based on these data, the subcutaneous injection was selected as the main therapeutic method of Glypin administration; the minimal effective dose for Glypin preclinical study was established as 100 μg/kg body mass, and a single dose for human treatment was defined as 0.75 and 1.5 mg. The intranasal introduction of Glypin was observed to have a statistically reliable positive effect on the cognitive capacities of a mouse with Alzheimer’s disease model. The similarity of the characteristics of Glypin and Lixumia shown in our study make it possible to expect that they will have equal therapeutic efficacy with daily use of a single dose.
作者简介
E. Sannikova
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
俄罗斯联邦, Moscow, 117545
N. Bobkova
Institute of Cell Biophysics, Russian Academy of Sciences
Email: dg_kozlov@genetika.ru
俄罗斯联邦, Pushchino, Moscow oblast, 142290
O. Tatarnikova
Institute of Cell Biophysics, Russian Academy of Sciences
Email: dg_kozlov@genetika.ru
俄罗斯联邦, Pushchino, Moscow oblast, 142290
S. Yarotskii
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
俄罗斯联邦, Moscow, 117545
E. Askerova
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
俄罗斯联邦, Moscow, 117545
N. Rykalina
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
俄罗斯联邦, Moscow, 117545
V. Yurin
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
俄罗斯联邦, Moscow, 117545
T. Gracheva
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
俄罗斯联邦, Moscow, 117545
F. Klebanov
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
俄罗斯联邦, Moscow, 117545
I. Zalunin
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
俄罗斯联邦, Moscow, 117545
S. Cheperegin
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
俄罗斯联邦, Moscow, 117545
N. Bulushova
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
Email: dg_kozlov@genetika.ru
俄罗斯联邦, Moscow, 117545
D. Kozlov
State Research Institute for Genetics and Selection of Industrial Microorganisms of the National Research Center,Kurchatov Institute (GOSNIIGENETIKA, NRC, Kurchatov Institute)
编辑信件的主要联系方式.
Email: dg_kozlov@genetika.ru
俄罗斯联邦, Moscow, 117545
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