NNC0640

NNC0640 Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  NNC0640 is a negative allosteric modulator of glucagon-like peptide-1 receptor (GLP-1R).

• in vitro

  Crystal structures of the human GLP-1R transmembrane domain in complex with two different negative allosteric modulators, PF-06372222 and NNC0640, at 2.7 and 3.0 ? resolution, respectively were reported. The structures reveal a common binding pocket for negative allosteric modulators, present in both GLP-1R and GCGR and located outside helices V-VII near the intracellular half of the receptor. The receptor is in an inactive conformation with compounds that restrict movement of the intracellular tip of helix VI, a movement that is generally associated with activation mechanisms in class A GPCRs. Molecular modelling and mutagenesis studies indicate that agonist positive allosteric modulators target the same general region, but in a distinct sub-pocket at the interface between helices V and VI, which may facilitate the formation of an intracellular binding site that enhances G-protein coupling._x000D_ _x000D_ Reference: Song G, Yang D, Wang Y, de Graaf C, Zhou Q, Jiang S, Liu K, Cai X, Dai A, Lin G, Liu D, Wu F, Wu Y, Zhao S, Ye L, Han GW, Lau J, Wu B, Hanson MA, Liu ZJ, Wang MW, Stevens RC. Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators. Nature. 2017 Jun 8;546(7657):312-315. doi: 10.1038/nature22378. Epub 2017 May 17. PMID: 28514449.

• target

  Glucagon receptors (pKi = 7.4).

• Lager

  Store at -20°C

NNC0640 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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