title: BF066, a novel dual target antiplatelet agent without significant bleeding.
abstract: In this study, we report BF066, a novel adenine derivative, inhibits platelet activation and thrombosis via the adenosine receptor (A(2A)) activation and phosphodiesterase (PDE) inhibition. BF066 inhibits platelet aggregation and ATP releasing induced by multiple platelet agonists in a dose-dependent manner. The inhibition of BF066 on ADP-induced aggregation is potentiated by adenosine and can be dramatically antagonized by the A(2A) antagonist SCH58261. BF066 also inhibits the PDE activity and platelet spreading on fibrinogen. In FeCl(3)-injured mouse mesenteric arterial thrombosis model, BF066 prevents thrombus formation effectively, similar to clopidogrel. Intriguingly, at dose achieving similar antithrombotic effect compared to clopidogrel, BF066 does not increase bleeding significantly. Taken together, these results suggest that BF066 may be an effective and safe antiplatelet agent targeting both PDE and A(2A). Considering the successful use of combined antiplatelet therapy, BF066 may be further developed as a novel dual target antiplatelet agent.
authors: School of Life Science, Fudan University, Shanghai, China.
authors: ChangE
authors: C
authors: Pan
authors: Xunbin
authors: X
authors: Wei
authors: Jianqin
authors: J
authors: Ye
authors: Guangda
authors: G
authors: Liu
authors: Si
authors: S
authors: Zhang
authors: Yan
authors: Y
authors: Zhang
authors: Hongguang
authors: H
authors: Du
authors: Zhongren
authors: Z
authors: Ding
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000225:Adenine / Q000009:adverse effects* / Q000494:pharmacology*; D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D002712:Chlorides / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D055767:Immobilized Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000494:pharmacology*; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D013927:Thrombosis / Q000139:chemically induced
chemical_list: C579115:2-methylthio-6-phenethylaminoadenosine; D002712:Chlorides; D005290:Ferric Compounds; D055767:Immobilized Proteins; D009842:Oligopeptides; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D043705:Receptor, Adenosine A2A; C455901:alanyl-tyrosyl-prolyl-glycyl-lysyl-phenylalanine; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D005340:Fibrinogen; D003094:Collagen; D010727:Phosphoric Diester Hydrolases; D013917:Thrombin; D000225:Adenine; D000241:Adenosine; C024555:ferric chloride