A continued saga of Boc5, the first non-peptidic glucagon-like peptide-1 receptor agonist with in vivo activities.
Glucagon-like peptide-1 (GLP-1)-based therapy presents a promising option for treating type 2 diabetes. However, there are several limitations relative to the peptidic GLP-1 mimetics currently on the market or under development. This concern has led to a continued interest in the search for non-peptidic agonists for GLP-1 receptor (GLP-1R). Here, we briefly review the discovery, characterization and current status of a novel class of cyclobutane-derivative-based non-peptidic agonists for GLP-1R, including Boc5 and its newly discovered analogue WB4-24. Although the oral bioavailability of such compounds still poses great challenges, the progress made so far encourages us to identify a truly 'druggable' small molecule agonist for GLP-1R.
National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Min
M
He
Ni
N
Guan
Wei-wei
WW
Gao
Qing
Q
Liu
Xiao-yan
XY
Wu
Da-wei
DW
Ma
Da-fang
DF
Zhong
Guang-bo
GB
Ge
Chuan
C
Li
Xiao-yan
XY
Chen
Ling
L
Yang
Jia-yu
JY
Liao
Ming-wei
MW
Wang
D000818:Animals; D003503:Cyclobutanes / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D018027:Receptors, Glucagon / Q000819:agonists*
C533559:Boc5 compound; D003503:Cyclobutanes; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1