2424-90-0Relevant articles and documents
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Bernhard,Albrecht
, p. 977,979,985 (1948)
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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 (2021/01/13)
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).
Biosynthesis of defensive coccinellidae alkaloids: Incorporation of fatty acids in adaline, coccinelline, and harmonine
Haulotte, Eveline,Laurent, Pascal,Braekman, Jean-Claude
, p. 1907 - 1912 (2012/05/31)
In this study, we report on in vitro incorporation experiments of several labelled fatty acids in the ladybird alkaloids coccinelline (Coccinella 7-punctata), adaline (Adalia 2-punctata), and harmonine (Harmonia axyridis). The obtained results clearly indicate that stearic acid is the precursor of coccinelline and harmonine, whereas myristic acid is at the origin of the carbon skeleton of adaline. Possible pathways for the biosynthesis of these alkaloids are presented. In vitro incorporation experiments of labelled fatty acids in the ladybird alkaloids coccinelline (Coccinella 7-punctata), adaline (Adalia 2-punctata) and harmonine (Harmonia axyridis) indicate that stearicacid is the best precursor for the biosynthesis of coccinelline and harmonine, whereas myristic acid is more efficient for the formation of the carbon skeleton of adaline. Copyright
One-step Synthesis of Long-chain Aliphatic α,ω-Dicarboxylic Acids Utilizing the Copper-catalyzed Reaction of β-Propiolactone with α,ω-Di-Grignard Reagents
Fujisawa, Tamotsu,Sato, Toshio,Kawara, Tatsuo,Tago, Hideyuki
, p. 345 - 346 (2007/10/02)
Copper-catalyzed reaction of β-propiolactone with α,ω-di-Grignard reagents, followed by esterification gave six-carbon homologated α,ω-dicarboxylic acid esters in good yields.
