1、%臺(%臻(覄%臼(倀%臽(簀%臾(鯯簀%臿(怈%舀(祗%舁(%舂(喸%舃(%舄(%舅(%舆(%與(%興(娲谀%舉(%舊(%舋(%舌(%舍(栀%舎(鐀%舏(%舐(%舑(%舒(%舓(%舔(綌鰀%舕(%舖(%舗(%舘(%舙(%舚(%舛(單%舜(%舝(吀%舞(%舟(继%舠(%舡(%舢(酯尀%舣(尀%舤(蠀%舥(迭%舦(%舧(搀%舨(退%舩(网%航(%舫(%般(稄%舭(%舮(頀%舯(%舰(%舱(%舲(漌%舳(琀%舴(%舵(%舶(倀%舷(练倀%舸(%船(%舺(%舻(%舼(噺%舽(堀%舾(佚%舿(%艀(%艁(喞怀%艂(釋谀%艃(谀%艄(%艅(樑%艆(栀%艇(栀%艈(栀%艉(囔鐀%艊(斱%艋(槍%艌(%艍(
2、%艎(%艏(鮽%艐(%艑(苟%艒(%艓(砀%艔(砀%艕(%艖(%艗(%艘(怔耀%艙(訓耀%艚(耀%艛(%艜(史%艝(%艞(蠀%艟(%艠(退%艡(退%艢(镣退%艣(%艤(%艥(%艦(%艧(頀%艨(頀%艩(皪%艪(%艫(%艬(%艭(%艮(%良(釂%艰(髪%艱(嗔簀%色(藿%艳(%艴(%艵(%艶(%艷(%艸(怀%艹(%艺(鰐%艻(%艼(栀%艽(栀%艾(泸栀%艿(栀%芀(栀%芁(浬鐀%节(%芃(瀀%芄(瀀%芅(%芆(伈%芇(%芈(%芉(%芊(砀%芋(%芌(%芍(%芎(%芏(%芐(%芑(%芒(节%芓(%芔(尀%芕(蠀%芖(%芗(%芘(嗊%芙(%芚(退%芛(%芜(%芝(%芞(%芟(辽%芠(氀%芡(頀%芢(
3、頀%芣(%芤(%芥(嵯%芦(%芧(%芨(%芩(岣%芪(簀%芫(簀%芬(%芭(%芮(鰲%芯(堀%芰(萀%花(萀%芲(顊%芳(%芴(要怀%芵(%芶(%芷(%芸(Screening Librarieswww.MedChemE1administration of 300 mol/kg JNJ-42041935, the bioluminescence over the peritoneal area is increased by 2.2 0.3-fold relative to luciferase-treated vehicle controls in the mouse 1.PROTOCOLKi
4、nase Assay 1 The potency of JNJ-42041935 for inhibition of the structurally related enzyme FIH is assessed by methods similar to those described for PHD2. In brief, activity of FIH is determined using purified glutathione transferase-tagged full-length FIH amino acids 1 to 350 and a synthetic HIF-1 peptide corresponding to residues Asp788 to Leu822. Compounds are preincubated with 17.1 nM FIH for 30 min, followed by a 10-min incubation with 1 M 2-14C2-oxoglutarate, in the presence of
