Danuglipron — pharmacology
Molecular targets, mechanism of action, pharmacokinetics and interactions as characterised in humans.
§2Pharmacology
§2.1Molecular targets
Table 2. Molecular targets recorded for Danuglipron, with the character of the interaction and the potency where the Institute holds it.
| Target | Interaction | Note |
|---|---|---|
| GLP-1 receptor (GLP1R) | Agonist | Orthosteric-adjacent binding; full cyclic-AMP efficacy reported in vitro |
§2.2Mechanism of action
Small-molecule GLP-1 receptor agonism with a short half-life requiring twice-daily administration. The Institute includes this monograph specifically because a discontinued programme is evidence, and because the reasons for discontinuation — tolerability at effective doses and a hepatic signal — are directly relevant to the interpretation of other oral non-peptide agents in development.[1,2]
§2.3Pharmacokinetics
- Terminal half-life
- ≈4–5 h
- Time to maximum concentration
- 2–4 h
- Volume of distribution
- not published
- Plasma protein binding
- high
- Clearance
- not published
- Bioavailability
- adequate for oral dosing
Hepatic metabolism. The short half-life necessitated twice-daily dosing, which the Institute notes contributed to the tolerability profile by producing repeated peak exposures.
§2.4Interactions
- Not fully characterised
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Saxena AR, Frias JP, Brown LS, Gorman DN, Vasas S, Tsamandouras N, Birnbaum MJ. Efficacy and safety of oral small molecule glucagon-like peptide 1 receptor agonist danuglipron for glycemic control among patients with type 2 diabetes: a randomized clinical trial. JAMA Network Open 2023;6(5):e2314493. doi:10.1001/jamanetworkopen.2023.14493 · PMID 37237090
- Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metabolism 2018;27(4):740–756. doi:10.1016/j.cmet.2018.03.001 · PMID 29617641
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.