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More recently, a small-molecule APJ agonist partnered with BioAge failed in clinical development due to hepatotoxicity unrelated to target engagement, highlighting that off-target toxicity can arise independently of the signaling bias hypothesis (Ryffel et al., 2023)

Thus, based on the results of CV outcomes trials with incretin-based agents, clinical priority of GLP-1RAs may be accentuated when choosing antidiabetic agents, at least for T2D patients at higher risk of CV events

Given the significant therapeutic value of this mechanism, we pursued a novel high-throughput screening strategy that identified a series of small-molecule GLP-1R agonist leads

The big difference in dose is questionable, and there is no definite explanation for it

Structural analogs of suramin, such as Evans blue and trypan blue, also share the molecular features necessary for TNF interaction