molecules of the month


GLP-1R/GLP molecular glue agonist (PAM)

oral blood glucose↓, additive w/ sitaglipin

from 220k cmpd cell-based screen + PK opt.

J. Med. Chem., Mar. 15, 2021

Lilly Research Laboratories, Indianapolis, IN

1 min read

1.The Lilly glucagon-like peptide-1 receptor (GLP-1R) agonist (LSN3318839) is a positive allosteric modulator intended to treat type 2 diabetes. This drug candidate has an interesting proposed mechanism as a molecular glue between GLP-1R and GLP peptide, enhancing endogenous peptide activity. The starting point was identified from a 220k compound cell-based screen in the presence of GLP-1 peptide, and optimization of PK of prior lead LSN3160440 led to LSN3318839. Oral administration of LSN3318839 (30 mg/kg) results in a blood glucose lowering effect in animal models, which is additive with sitaglipin administration. It is the first characterized molecular glue for GPCRs with demonstrated in vivo efficacy.

request a trial

Drug Hunter is commited to helping industry innovators make informed decisions. Premium members have access to our library of the latest stories in science, written by scientists.

Request a trial to access insights powering the pros in our industry.

already a member? log in: