Category Archives: GPCR ligands

Improving Solubility using X-ray crystal structure data


A recent publication from AstraZeneca provides a really interesting overview of the approach that they took to optimise the solubility of a series of GPR119 agonists. The initial lead compound 2 was only poorly soluble but, by obtaining small molecule … Continue reading

Posted in GPCR ligands, Med Chem Strategy | Tagged , , , | 6 Comments

GPCR structure and modeling


A recently published letter from scientists at Boehringer Ingelheim nicely summarizes recent advances in our understanding of G protein-coupled receptor (GPCR) structure and function. X-ray structures of the inactive forms of bovine rhodopsin (2000), β2 adrenergic receptor (2007 – with antibody … Continue reading

Posted in Computational Methods, GPCR ligands | Tagged , , , , , , , , , , | 1 Comment

Discovery of MK-2918 (CGRP Antagonist)


The triptan drugs have been highly successful in the treatment of migraine, but adverse effects and low responder rates in some patients have provided the impetus to develop alternative therapies.   Blockers of the calcitonin gene-related peptide (CGRP) receptor have … Continue reading

Posted in GPCR ligands | Tagged , , , , , , , , , , | Leave a comment

Discovery of PF-232798 (CCR5 Antagonist)


CCR5 antagonists prevent entry of HIV into host cells by binding to the CCR5 co-receptor and stopping the gp120-CD4 complex from making the crucial interaction with CCR5 that leads to fusion of the viral and host cell membranes (see Wikipedia article … Continue reading

Posted in Clinical Candidates, GPCR ligands | Tagged , , , , , , , , , , , , , , , , , | Leave a comment