Abstract
The discovery and optimization of a novel series of GPR142 agonists are described. These led to the identification of compound 21 (LY3325656), which demonstrated anti-diabetic benefits in pre-clinical studies and ADME/PK properties suitable for human dosing. Compound 21 is the first GPR142 agonist molecule advancing to phase 1 clinic trials for the treatment of Type 2 diabetes.
Keywords:
GPR142 agonist; Glucose-dependent insulin secretion; Metabolism; Type 2 diabetes.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Benzamides / chemical synthesis
-
Benzamides / pharmacokinetics
-
Benzamides / therapeutic use*
-
Diabetes Mellitus, Experimental / drug therapy*
-
Dogs
-
Drug Discovery
-
Drug Evaluation, Preclinical
-
Gene Knockout Techniques
-
Humans
-
Hypoglycemic Agents / chemical synthesis
-
Hypoglycemic Agents / pharmacokinetics
-
Hypoglycemic Agents / therapeutic use*
-
Mice, Knockout
-
Molecular Structure
-
Rats
-
Receptors, G-Protein-Coupled / agonists*
-
Receptors, G-Protein-Coupled / genetics
-
Structure-Activity Relationship
-
Triazoles / chemical synthesis
-
Triazoles / pharmacokinetics
-
Triazoles / therapeutic use*
Substances
-
Benzamides
-
GPR142 protein, human
-
GPR142 protein, mouse
-
Hypoglycemic Agents
-
Receptors, G-Protein-Coupled
-
Triazoles