Woolford_2016_J.Med.Chem_59_5356

Reference

Title : Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Discovered through X-ray Fragment Screening - Woolford_2016_J.Med.Chem_59_5356
Author(s) : Woolford AJ , Pero JE , Aravapalli S , Berdini V , Coyle JE , Day PJ , Dodson AM , Grondin P , Holding FP , Lee LY , Li P , Manas ES , Marino J, Jr. , Martin AC , McCleland BW , McMenamin RL , Murray CW , Neipp CE , Page LW , Patel VK , Potvain F , Rich S , Rivero RA , Smith K , Somers DO , Trottet L , Velagaleti R , Williams G , Xie R
Ref : Journal of Medicinal Chemistry , 59 :5356 , 2016
Abstract : Elevated levels of human lipoprotein-associated phospholipase A2 (Lp-PLA2) are associated with cardiovascular disease and dementia. A fragment screen was conducted against Lp-PLA2 in order to identify novel inhibitors. Multiple fragment hits were observed in different regions of the active site, including some hits that bound in a pocket created by movement of a protein side chain (approximately 13 A from the catalytic residue Ser273). Using structure guided design, we optimized a fragment that bound in this pocket to generate a novel low nanomolar chemotype, which did not interact with the catalytic residues.
ESTHER : Woolford_2016_J.Med.Chem_59_5356
PubMedSearch : Woolford_2016_J.Med.Chem_59_5356
PubMedID: 27167608
Gene_locus related to this paper: human-PLA2G7

Related information

Gene_locus related to this paper: human-PLA2G7

Citations formats

Woolford AJ, Pero JE, Aravapalli S, Berdini V, Coyle JE, Day PJ, Dodson AM, Grondin P, Holding FP, Lee LY, Li P, Manas ES, Marino J, Jr., Martin AC, McCleland BW, McMenamin RL, Murray CW, Neipp CE, Page LW, Patel VK, Potvain F, Rich S, Rivero RA, Smith K, Somers DO, Trottet L, Velagaleti R, Williams G, Xie R (2016)
Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Discovered through X-ray Fragment Screening
Journal of Medicinal Chemistry 59 :5356

Woolford AJ, Pero JE, Aravapalli S, Berdini V, Coyle JE, Day PJ, Dodson AM, Grondin P, Holding FP, Lee LY, Li P, Manas ES, Marino J, Jr., Martin AC, McCleland BW, McMenamin RL, Murray CW, Neipp CE, Page LW, Patel VK, Potvain F, Rich S, Rivero RA, Smith K, Somers DO, Trottet L, Velagaleti R, Williams G, Xie R (2016)
Journal of Medicinal Chemistry 59 :5356