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| | NNC0640 Basic information |
| Product Name: | NNC0640 | | Synonyms: | NNC0640;Benzamide, 4-[[(4-cyclohexylphenyl)[[[3-(methylsulfonyl)phenyl]amino]carbonyl]amino]methyl]-N-2H-tetrazol-5-yl-;NNC-0640,Glucagon Receptor,NNC0640,GCGR,inhibit,Inhibitor,NNC 0640;4-((1-(4-Cyclohexylphenyl)-3-(3-(methylsulfonyl)phenyl)ureido)methyl)-N-(1H-tetrazol-5-yl)benzamide | | CAS: | 307986-98-7 | | MF: | C29H31N7O4S | | MW: | 573.67 | | EINECS: | | | Product Categories: | | | Mol File: | 307986-98-7.mol |  |
| | NNC0640 Chemical Properties |
| storage temp. | Store at -20°C | | solubility | DMSO:57.37(Max Conc. mg/mL);100.0(Max Conc. mM) | | form | Solid | | color | White to off-white |
| | NNC0640 Usage And Synthesis |
| Description | 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_
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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). | | storage | Store at -20°C |
| | NNC0640 Preparation Products And Raw materials |
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