Woolford_2016_J.Med.Chem_59_10738

Reference

Title : Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) - Woolford_2016_J.Med.Chem_59_10738
Author(s) : Woolford AJ , Day PJ , Beneton V , Berdini V , Coyle JE , Dudit Y , Grondin P , Huet P , Lee LY , Manas ES , McMenamin RL , Murray CW , Page LW , Patel VK , Potvain F , Rich SJ , Sang Y , Somers DO , Trottet L , Wan Z , Zhang X
Ref : Journal of Medicinal Chemistry , 59 :10738 , 2016
Abstract : Lp-PLA2 has been explored as a target for a number of inflammation associated diseases, including cardiovascular disease and dementia. This article describes the discovery of a new fragment derived chemotype that interacts with the active site of Lp-PLA2. The starting fragment hit was discovered through an X-ray fragment screen and showed no activity in the bioassay (IC50 > 1 mM). The fragment hit was optimized using a variety of structure-based drug design techniques, including virtual screening, fragment merging, and improvement of shape complementarity. A novel series of Lp-PLA2 inhibitors was generated with low lipophilicity and a promising pharmacokinetic profile.
ESTHER : Woolford_2016_J.Med.Chem_59_10738
PubMedSearch : Woolford_2016_J.Med.Chem_59_10738
PubMedID: 27933945
Gene_locus related to this paper: human-PLA2G7

Related information

Gene_locus related to this paper: human-PLA2G7

Citations formats

Woolford AJ, Day PJ, Beneton V, Berdini V, Coyle JE, Dudit Y, Grondin P, Huet P, Lee LY, Manas ES, McMenamin RL, Murray CW, Page LW, Patel VK, Potvain F, Rich SJ, Sang Y, Somers DO, Trottet L, Wan Z, Zhang X (2016)
Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA2)
Journal of Medicinal Chemistry 59 :10738

Woolford AJ, Day PJ, Beneton V, Berdini V, Coyle JE, Dudit Y, Grondin P, Huet P, Lee LY, Manas ES, McMenamin RL, Murray CW, Page LW, Patel VK, Potvain F, Rich SJ, Sang Y, Somers DO, Trottet L, Wan Z, Zhang X (2016)
Journal of Medicinal Chemistry 59 :10738