Identification of a novel allosteric GLP-1R antagonist HTL26119 using structure- based drug design.
Bioorg Med Chem Lett
; 29(20): 126611, 2019 10 15.
Article
in En
| MEDLINE
| ID: mdl-31447084
ABSTRACT
A series of novel allosteric antagonists of the GLP-1 receptor (GLP-1R), exemplified by HTL26119, are described. SBDD approaches were employed to identify HTL26119, exploiting structural understanding of the allosteric binding site of the closely related Glucagon receptor (GCGR) (Jazayeri et al., 2016) and the homology relationships between GCGR and GLP-1R. The region around residue C3476.36b of the GLP-1R receptor represents a key difference from GCGR and was targeted for selectivity for GLP-1R.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glucagon-Like Peptide-1 Receptor
/
Heterocyclic Compounds
Type of study:
Diagnostic_studies
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2019
Document type:
Article