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CMD-05, a novel promising clinical anti-diabetic drug candidate, in vivo and vitro studies
Dipeptidyl peptidase IV (DPP-IV) inhibitor has been expected to be a new class of anti-diabetic agent. The present study was designed to characterize the pharmacological profiles of CMD-05, a novel DPP-IV inhibitor discovered in our laboratory, in vitro and in vivo. The IC(50) of CMD-05 on DPP-IV in...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390258/ https://www.ncbi.nlm.nih.gov/pubmed/28406239 http://dx.doi.org/10.1038/srep46628 |
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author | Ma, Jie Li, Huan Hu, Xiangnan Yang, Lu Chen, Qi Hu, Congli Chen, Zhihao Tian, Xiaoyan Yang, Yang Luo, Ying Gan, Run Yang, Junqing |
author_facet | Ma, Jie Li, Huan Hu, Xiangnan Yang, Lu Chen, Qi Hu, Congli Chen, Zhihao Tian, Xiaoyan Yang, Yang Luo, Ying Gan, Run Yang, Junqing |
author_sort | Ma, Jie |
collection | PubMed |
description | Dipeptidyl peptidase IV (DPP-IV) inhibitor has been expected to be a new class of anti-diabetic agent. The present study was designed to characterize the pharmacological profiles of CMD-05, a novel DPP-IV inhibitor discovered in our laboratory, in vitro and in vivo. The IC(50) of CMD-05 on DPP-IV inhibitory activity was approximately 12 nM while vildagliptin was 3.5 nM in vitro. In diabetes rat model established by high fat diet/low dose streptozotocin, CMD-05 inhibited DPP-IV activity, significantly improved glucose tolerance, increased GLP-1 and insulin levels in plasma. Long-term administration of CMD-05 decreased HbA1c and TG levels and improved the islet function without significantly effect on body weight. Furthermore, CMD-05 reduced INS-1 cell apoptosis and increased GLP-1 secretion in NCI-H716. After oral administration, CMD-05 reached peak concentration at 30 min with half-life of 288 minutes and the inhibitory rate of DPP-IV greater than 50% lasted for 15 h. In fasted normal rats, CMD-05 didn’t cause significant hypoglycemia. CMD-05 had a lower cytotoxicity than vildagliptin in vitro and its maximum tolerance dose in mice is beyond 2000 mg/kg. These results indicated that CMD-05 has similar activity with vildagliptin in vivo and has a much longer half-life and lower cytotoxicity than vildagliptin. |
format | Online Article Text |
id | pubmed-5390258 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53902582017-04-14 CMD-05, a novel promising clinical anti-diabetic drug candidate, in vivo and vitro studies Ma, Jie Li, Huan Hu, Xiangnan Yang, Lu Chen, Qi Hu, Congli Chen, Zhihao Tian, Xiaoyan Yang, Yang Luo, Ying Gan, Run Yang, Junqing Sci Rep Article Dipeptidyl peptidase IV (DPP-IV) inhibitor has been expected to be a new class of anti-diabetic agent. The present study was designed to characterize the pharmacological profiles of CMD-05, a novel DPP-IV inhibitor discovered in our laboratory, in vitro and in vivo. The IC(50) of CMD-05 on DPP-IV inhibitory activity was approximately 12 nM while vildagliptin was 3.5 nM in vitro. In diabetes rat model established by high fat diet/low dose streptozotocin, CMD-05 inhibited DPP-IV activity, significantly improved glucose tolerance, increased GLP-1 and insulin levels in plasma. Long-term administration of CMD-05 decreased HbA1c and TG levels and improved the islet function without significantly effect on body weight. Furthermore, CMD-05 reduced INS-1 cell apoptosis and increased GLP-1 secretion in NCI-H716. After oral administration, CMD-05 reached peak concentration at 30 min with half-life of 288 minutes and the inhibitory rate of DPP-IV greater than 50% lasted for 15 h. In fasted normal rats, CMD-05 didn’t cause significant hypoglycemia. CMD-05 had a lower cytotoxicity than vildagliptin in vitro and its maximum tolerance dose in mice is beyond 2000 mg/kg. These results indicated that CMD-05 has similar activity with vildagliptin in vivo and has a much longer half-life and lower cytotoxicity than vildagliptin. Nature Publishing Group 2017-04-13 /pmc/articles/PMC5390258/ /pubmed/28406239 http://dx.doi.org/10.1038/srep46628 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Ma, Jie Li, Huan Hu, Xiangnan Yang, Lu Chen, Qi Hu, Congli Chen, Zhihao Tian, Xiaoyan Yang, Yang Luo, Ying Gan, Run Yang, Junqing CMD-05, a novel promising clinical anti-diabetic drug candidate, in vivo and vitro studies |
title | CMD-05, a novel promising clinical anti-diabetic drug candidate, in vivo and vitro studies |
title_full | CMD-05, a novel promising clinical anti-diabetic drug candidate, in vivo and vitro studies |
title_fullStr | CMD-05, a novel promising clinical anti-diabetic drug candidate, in vivo and vitro studies |
title_full_unstemmed | CMD-05, a novel promising clinical anti-diabetic drug candidate, in vivo and vitro studies |
title_short | CMD-05, a novel promising clinical anti-diabetic drug candidate, in vivo and vitro studies |
title_sort | cmd-05, a novel promising clinical anti-diabetic drug candidate, in vivo and vitro studies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390258/ https://www.ncbi.nlm.nih.gov/pubmed/28406239 http://dx.doi.org/10.1038/srep46628 |
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