1118767-15-9Relevant articles and documents
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).
A METHOD FOR MODIFICATION OF PEPTIDES IMMOBILIZED ON A SOLID SUPPORT BY TRACELESS REDUCTIVELY CLEAVABLE LINKER MOLECULES
-
Page/Page column 58, (2021/02/12)
The present invention relates to a method for modifying and purifying peptides comprising an immobilizing step, a modification step and a releasing step. In the immobilizing step, a crude linker-tagged peptide L-P is coupled to a solid support yielding an immobilized linker-tagged peptide S-L-P. Subsequently, the immobilized linker-tagged peptide S-L-P is modified with one or more organic molecules yielding an immobilized linker-tagged peptide S-L-mP. Finally, the modified peptide is released via a reduced intermediate RI. The linker molecule is a compound of formula 1, X-Tbb-Vaa-U-Y-Z (1), which can be coupled to a purification resin via the moiety X and to a peptide via the moiety Y under the release of the leaving group Z. T is an optional spacer moiety and V is an optional electron withdrawing moiety. U is an aryl or 5- or 6-membered heteroaryl moiety bound to at least one electron withdrawing moiety V, W or E. The linker is stable under acidic conditions and releases the peptide upon addition of a reducing agent.
Novel GLP-1 Analogues
-
, (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.
ANTIBODY-COUPLED CYCLIC PEPTIDE TYROSINE TYROSINE COMPOUNDS AS MODULATORS OF NEUROPEPTIDE Y RECEPTORS
-
Paragraph 0511, (2018/05/17)
The present invention comprises conjugates comprising a monoclonal antibody conjugated to a cyclic PYY peptide. The invention also relates to pharmaceutical compositions and methods for use thereof. The novel conjugates are useful for preventing, treating or ameliorating diseases and disorders disclosed herein.
Protease stabilized acylated insulin analogues
-
, (2017/07/14)
Novel acylated insulin analoges exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analoges contain B25H and A14E or A14H.
