DBPR108, a novel dipeptidyl peptidase-4 inhibitor with antihyperglycemic activity
Copyright © 2021. Published by Elsevier Inc..
AIMS: Dipeptidyl peptidase 4 (DPP-4) is a valid molecular drug target from which its inhibitors have been developed as medicines for treating diabetes. The present study evaluated a new synthetic DPP-4-specific inhibitor of small molecule DBPR108 for pharmacology and pharmacokinetic profiles.
MAIN METHODS: DBPR108 of various doses was orally administered to rats, diabetic mice, and dogs and the systemic circulating DPP-4 activities in the animals were measured to demonstrate the pharmacological mechanisms of action via DPP-4 inhibition. Upon an oral administration of DBPR108, the serum active GLP-1 and insulin levels of the rats challenged with an oral glucose ingestion were measured. Oral glucose tolerance test in diet-induced obese mice was performed to examine if DBPR108 increases the glucose tolerability in animals.
KEY FINDINGS: Orally administered DBPR108 inhibited the systemic plasma DPP-4 activities in rats, dogs and diabetic mice in a dose-dependent manner. DBPR108 caused elevated serum levels of active GLP-1 and insulin in the rats. DBPR108 dose-dependently increased the glucose tolerability in diet-induced obese (DIO) mice and, furthermore, DIO mice treated with DBPR108 (0.1 mg/kg) in combination with metformin (50 or 100 mg/kg) showed a prominently strong increase in the glucose tolerability.
SIGNIFICANCE: DBPR108 is a novel DPP-4-selective inhibitor of small molecule that demonstrated potent in vivo pharmacological effects and good safety profiles in animals. DBPR108 is now a drug candidate being further developed in the clinical studies as therapeutics for treating diabetes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:278 |
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| Enthalten in: |
Life sciences - 278(2021) vom: 01. Aug., Seite 119574 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yeh, Kai-Chia [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.07.2021 Date Revised 30.07.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.lfs.2021.119574 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a DBPR108, a novel dipeptidyl peptidase-4 inhibitor with antihyperglycemic activity |
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| 500 | |a Date Completed 07.07.2021 | ||
| 500 | |a Date Revised 30.07.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021. Published by Elsevier Inc. | ||
| 520 | |a AIMS: Dipeptidyl peptidase 4 (DPP-4) is a valid molecular drug target from which its inhibitors have been developed as medicines for treating diabetes. The present study evaluated a new synthetic DPP-4-specific inhibitor of small molecule DBPR108 for pharmacology and pharmacokinetic profiles | ||
| 520 | |a MAIN METHODS: DBPR108 of various doses was orally administered to rats, diabetic mice, and dogs and the systemic circulating DPP-4 activities in the animals were measured to demonstrate the pharmacological mechanisms of action via DPP-4 inhibition. Upon an oral administration of DBPR108, the serum active GLP-1 and insulin levels of the rats challenged with an oral glucose ingestion were measured. Oral glucose tolerance test in diet-induced obese mice was performed to examine if DBPR108 increases the glucose tolerability in animals | ||
| 520 | |a KEY FINDINGS: Orally administered DBPR108 inhibited the systemic plasma DPP-4 activities in rats, dogs and diabetic mice in a dose-dependent manner. DBPR108 caused elevated serum levels of active GLP-1 and insulin in the rats. DBPR108 dose-dependently increased the glucose tolerability in diet-induced obese (DIO) mice and, furthermore, DIO mice treated with DBPR108 (0.1 mg/kg) in combination with metformin (50 or 100 mg/kg) showed a prominently strong increase in the glucose tolerability | ||
| 520 | |a SIGNIFICANCE: DBPR108 is a novel DPP-4-selective inhibitor of small molecule that demonstrated potent in vivo pharmacological effects and good safety profiles in animals. DBPR108 is now a drug candidate being further developed in the clinical studies as therapeutics for treating diabetes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DPP-4 | |
| 650 | 4 | |a Diabetes | |
| 650 | 4 | |a Dipeptidyl peptidase | |
| 650 | 4 | |a Drug discovery | |
| 650 | 7 | |a Butanes |2 NLM | |
| 650 | 7 | |a DBPR108 |2 NLM | |
| 650 | 7 | |a Dipeptidyl-Peptidase IV Inhibitors |2 NLM | |
| 650 | 7 | |a Hypoglycemic Agents |2 NLM | |
| 650 | 7 | |a Insulin |2 NLM | |
| 650 | 7 | |a Nitriles |2 NLM | |
| 650 | 7 | |a Pyrrolidines |2 NLM | |
| 650 | 7 | |a Metformin |2 NLM | |
| 650 | 7 | |a 9100L32L2N |2 NLM | |
| 650 | 7 | |a DPP4 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.14.5 |2 NLM | |
| 650 | 7 | |a Dipeptidyl Peptidase 4 |2 NLM | |
| 650 | 7 | |a EC 3.4.14.5 |2 NLM | |
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| 700 | 1 | |a Huang, Chung-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Chih-Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Min-Hsien |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yu-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Chou, Ling-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Ho, Hsuan-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Jen-Shin |e verfasserin |4 aut | |
| 700 | 1 | |a Hsu, Tsu |e verfasserin |4 aut | |
| 700 | 1 | |a Jiaang, Weir-Torn |e verfasserin |4 aut | |
| 700 | 1 | |a Chao, Yu-Sheng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chiung-Tong |e verfasserin |4 aut | |
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