Holding FP

References (1)

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