P
Paul John Dransfield
Researcher at Amgen
Publications - 36
Citations - 877
Paul John Dransfield is an academic researcher from Amgen. The author has contributed to research in topics: Agonist & Triazole. The author has an hindex of 13, co-authored 35 publications receiving 806 citations.
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Journal ArticleDOI
A potent class of GPR40 full agonists engages the enteroinsular axis to promote glucose control in rodents.
Jian Luo,Gayathri Swaminath,Sean P. Brown,Jane Zhang,Qi Guo,Michael Chen,Kathy Nguyen,Thanhvien Tran,Lynn Miao,Paul John Dransfield,Marc Vimolratana,Jonathan B. Houze,Simon Wong,Maria M. Toteva,Bei Shan,Frank Li,Run Zhuang,Daniel C.-H. Lin +17 more
TL;DR: GPR40 full agonists AM-1638 and AM-6226 stimulate GLP-1 and GIP secretion from intestinal enteroendocrine cells and increase GSIS from pancreatic islets, leading to enhanced glucose control in the high fat fed, streptozotocin treated and NONcNZO10/LtJ mouse models of type 2 diabetes.
Journal ArticleDOI
Identification and pharmacological characterization of multiple allosteric binding sites on the free fatty acid 1 receptor.
Daniel C.-H. Lin,Qi Guo,Jian Luo,Jane Zhang,Kathy Nguyen,Michael Chen,Thanh Tran,Paul John Dransfield,Sean P. Brown,Jonathan B. Houze,Marc Vimolratana,Xian Yun Jiao,Yingcai Wang,Nigel J. M. Birdsall,Gayathri Swaminath +14 more
TL;DR: There appear to be three allosterically linked binding sites on FFA1 with agonists specific for each of these sites, and these ligands with their high potencies and strong positive functional cooperativity with endogenous fatty acids have the potential to deliver therapeutic benefits.
Journal ArticleDOI
Activation of FFA1 mediates GLP-1 secretion in mice. Evidence for allosterism at FFA1.
Yumei Xiong,Gayathri Swaminath,Qiong Cao,Li Yang,Qi Guo,Heather Salomonis,Jenny Ying-Lin Lu,Jonathan B. Houze,Paul John Dransfield,Yingcai Wang,Jiwen Jim Liu,Simon Wong,Ralf Schwandner,Franziska Steger,Helene Baribault,Lily Liu,Suzanne Coberly,Lynn Miao,Jane Zhang,Daniel C.-H. Lin,Margrit Schwarz +20 more
TL;DR: It is shown that allosterism at FFA1 can contribute to postprandial glucose management by stimulating insulin secretion via an extrapancreatic mechanism of action, and that GPR120 in GLP-1 secretion requires further investigation.
Journal ArticleDOI
Discovery of AM-1638: A Potent and Orally Bioavailable GPR40/FFA1 Full Agonist.
Sean P. Brown,Paul John Dransfield,Marc Vimolratana,Xianyun Jiao,Liusheng Zhu,Vatee Pattaropong,Ying Sun,Jinqian Liu,Jian Luo,Jane Zhang,Simon Wong,Run Zhuang,Qi Guo,Frank Li,Julio C. Medina,Gayathri Swaminath,Daniel C.-H. Lin,Jonathan B. Houze +17 more
TL;DR: The optimization from the G PR40 partial agonist 1 to the structurally and pharmacologically distinct GPR40 full agonist AM-1638 (21) is presented and the improved in vivo efficacy that GPR 40 full agonists 21 exhibits in BDF/DIO mice as compared to partial agonists 1.
Journal ArticleDOI
Discovery and Optimization of Potent GPR40 Full Agonists Containing Tricyclic Spirocycles
Yingcai Wang,Jiwen Jim Liu,Paul John Dransfield,Liusheng Zhu,Zhongyu Wang,Xiaohui Du,Xianyun Jiao,Yongli Su,An-Rong Li,Sean P. Brown,Annie Kasparian,Marc Vimolratana,Ming Yu,Vatee Pattaropong,Jonathan B. Houze,Gayathri Swaminath,Thanhvien Tran,Khanh Nguyen,Qi Guo,Jane Zhang,Run Zhuang,Frank Li,Lynn Miao,Michael D. Bartberger,Tiffany L. Correll,David Chow,Simon Wong,Jian Luo,Daniel C.-H. Lin,Julio C. Medina +29 more
TL;DR: The discovery of GPR40 full agonists containing conformationally constrained tricyclic spirocycles and their structure-activity relationships leading to more potent agonists such as AM-5262 with improved rat PK profile and general selectivity profile are presented.