![Fmoc-L-Lys[C20-OtBu-γ-Glu(OtBu)-AEEA-AEEA]-OH](/upload/2026/7/89-1.jpg "Fmoc-L-Lys[C20-OtBu-γ-Glu(OtBu)-AEEA-AEEA]-OH")
1169630-40-3Relevant academic research and scientific papers
Engineering of Orally Available, Ultralong-Acting Insulin Analogues: Discovery of OI338 and OI320
Kjeldsen, Thomas B.,Hubálek, Franti?ek,Tagmose, Tina M.,Pridal, Lone,Refsgaard, Hanne H. F.,Porsgaard, Trine,Gram-Nielsen, Sanne,Hovgaard, Lars,Valore, Henrik,Münzel, Martin,Hj?rringgaard, Claudia U.,Jeppesen, Claus Bekker,Manfè, Valentina,Hoeg-Jensen, Thomas,Ludvigsen, Svend,Nielsen, Peter Kresten,Lautrup-Larsen, Inger,Stidsen, Carsten E.,Wulff, Erik M.,Garibay, Patrick W.,Kodra, János T.,Nishimura, Erica,Madsen, Peter
, p. 616 - 628 (2021)
Recently, the first basal oral insulin (OI338) was shown to provide similar treatment outcomes to insulin glargine in a phase 2a clinical trial. Here, we report the engineering of a novel class of basal oral insulin analogues of which OI338, 10, in this publication, was successfully tested in the phase 2a clinical trial. We found that the introduction of two insulin substitutions, A14E and B25H, was needed to provide increased stability toward proteolysis. Ultralong pharmacokinetic profiles were obtained by attaching an albumin-binding side chain derived from octadecanedioic (C18) or icosanedioic acid (C20) to the lysine in position B29. Crucial for obtaining the ultralong PK profile was also a significant reduction of insulin receptor affinity. Oral bioavailability in dogs indicated that C18-based analogues were superior to C20-based analogues. These studies led to the identification of the two clinical candidates OI338 and OI320 (10 and 24, respectively).
Novel GLP-1 Analogues
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, (2019/10/20)
The present disclosure pertains to novel Glucagon like Peptide-1 (GLP-1) (7-37) analogs having an amino acid sequence with Leu or Ile at the C-terminal. The new analogs are potent GLP-1 agonists with reduced adverse effect and improved duration of action. The present disclosure further relates to acylated derivatives of the new analogs which have further improved potency and duration of action and are suitable for oral administration. The analogs of present disclosure may be useful in treatment of diabetes and obesity.
![18-[[(1S)-1-carboxy-4-[2-[2-[2-[2-[2-[2-(2,5-dioxopyrrolidin-1-yl)oxy-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-4-oxobutyl]amino]-18-oxooctadecanoic acid](/upload/2026/7/2ae95f5a-3c8e-4da9-b68c-81da25d7af55.png)
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