ArticleScientific reports2016
Intestinally-targeted TGR5 agonists equipped with quaternary ammonium have an improved hypoglycemic effect and reduced gallbladder filling effect.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 55 citations in OpenAlex.
- Rational Design and Evaluation of Novel TGR5 Agonists for Diabetes.Molecules (Basel, Switzerland) · 2026Article
- From chemical composition to clinical application: the value of bile-based traditional Chinese medicines in the treatment of liver diseases.Frontiers in pharmacology · 2026Review
- Bile Acids and Type 2 Diabetes: Roles in Glucose Homeostasis and Therapeutic Opportunities.Metabolites · 2025Review
- Bile acids and gestational diabetes mellitus: exploring the link and implications - a review.Frontiers in endocrinology · 2025Review
- Recent advancements in the structural exploration of TGR5 agonists for diabetes treatment.RSC medicinal chemistry · 2024Review
- Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Host-microbiome orchestration of the sulfated metabolome.Nature chemical biology · 2024Review
- TGR5 agonist inhibits intestinal epithelial cell apoptosis via cAMP/PKA/c-FLIP/JNK signaling pathway and ameliorates dextran sulfate sodium-induced ulcerative colitis.Acta pharmacologica Sinica · 2023Article
- The 16α-hydroxylated Bile Acid, Pythocholic Acid Decreases Food Intake and Increases Oleoylethanolamide in Male Mice.Endocrinology · 2023Article
- Trust Your Gut: Strategies and Tactics for Intestinally Restricted Drugs.ACS medicinal chemistry letters · 2023Review
- Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology.Nature reviews. Gastroenterology & hepatology · 2022Review
- Article
- Learn from failures and stay hopeful to GPR40, a GPCR target with robust efficacy, for therapy of metabolic disorders.Frontiers in pharmacology · 2022Review
- Bile acids-gut microbiota crosstalk contributes to the improvement of type 2 diabetes mellitus.Frontiers in pharmacology · 2022Review
- Intestinal Co-culture System to Study TGR5 Agonism and Gut Restriction.Bio-protocol · 2021Article
- The Liver under the Spotlight: Bile Acids and Oxysterols as Pivotal Actors Controlling Metabolism.Cells · 2021Review
- Bariatric surgery reveals a gut-restricted TGR5 agonist with anti-diabetic effects.Nature chemical biology · 2021Article
- (E)-7-Ethylidene-lithocholic Acid (7-ELCA) Is a Potent Dual Farnesoid X Receptor (FXR) Antagonist and GPBAR1 Agonist Inhibiting FXR-Induced Gene Expression in Hepatocytes and Stimulating Glucagon-like Peptide-1 Secretion From Enteroendocrine Cells.Frontiers in pharmacology · 2021Article
- The Physiological Importance of Bile Acid Structure and Composition on Glucose Homeostasis.Current diabetes reports · 2020Review
- GPBAR1 Activation by C6-Substituted Hyodeoxycholane Analogues Protect against Colitis.ACS medicinal chemistry letters · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TGR5 activation of enteroendocrine cells increases glucagon-like peptide 1 (GLP-1) release, which maintains glycemic homeostasis. However, TGR5 activation in the gallbladder and heart is associated with severe side effects. Therefore, intestinally-targeted TGR5 agonists were suggested as potential hypoglycemic agents with minimal side effects. However, until now no such compounds with robust glucose-lowering effects were reported, especially in diabetic animal models. Herein, we identify a TGR5 agonist, 26a, which was proven to be intestinally-targeted through pharmacokinetic studies. 26a was used as a tool drug to verify the intestinally-targeted strategy. 26a displayed a robust and long-lasting hypoglycemic effect in ob/ob mice (once a day dosing (QD) and 18-day treatment) owing to sustained stimulation of GLP-1 secretion, which suggested that robust hypoglycemic effect could be achieved with activation of TGR5 in intestine alone. However, the gallbladder filling effect of 26a was rather complicated. Although the gallbladder filling effect of 26a was decreased in mice after once a day dosing, this side effect was still not eliminated. To solve the problem above, several research strategies were raised for further optimization.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.