NNC0640

NNC0640 is a synthetic small-molecule negative allosteric modulator of class B G protein-coupled receptors in the glucagon subfamily, primarily targeting the human glucagon receptor (GCGR) and also acting at the glucagon‑like peptide‑1 receptor (GLP‑1R). It binds to an external site on the transmembrane domain, between helices VI and VII on the cytoplasmic-facing side, where it forms specific hydrogen bonds and hydrophobic contacts that stabilize the receptors in an inactive conformation and prevent the conformational changes required for G‑protein coupling and cAMP signaling. NNC0640 has been widely used as a tool compound to characterize GCGR and GLP‑1R structure, allosteric binding pockets, and signaling mechanisms, including in high‑resolution crystal structures of the receptors, and is primarily developed and supplied for research use in metabolic and diabetes-related biology rather than as a clinical therapeutic.[1][3][7]

Other names

NNC-0640NNC0640NNC 0640