Hormonal
Small-molecule ago-allosteric modulators of the GLP-1 receptor stimulate glucose-dependent insulin secretion and potentiate endogenous GLP-1 effects without altering GLP-1 potency, offering a potential pathway for orally active diabetes treatments.
This research describes a new class of small molecules that activate the GLP-1 receptor. Currently, these are experimental compounds tested in lab settings (cells and animal tissues). They stimulate insulin release in a glucose-dependent manner, similar to the natural hormone GLP-1, but via a different binding mechanism (allosteric). This is a foundational discovery for developing oral diabetes medications, but no such drug is currently available for human use based on this text.
These compounds act as both allosteric activators of the receptor and independent agonists... The most potent compound identified stimulates glucose-dependent insulin release from normal mouse islets but, importantly, not from GLP-1 receptor knockout mice.
Why this rating
High-quality biochemical and cellular assays (cAMP, binding, perfused pancreas) but lacks in vivo animal or human clinical data.
Source
Small-molecule agonists for the glucagon-like peptide 1 receptor
Lotte Bjerre Knudsen et al. · Proceedings of the National Academy of Sciences · 2007
DOI 10.1073/pnas.0605701104
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