• 提示：詳情請下載說明書。

• 產(chǎn)品描述： Verinurad (RDEA3170)是URAT1轉(zhuǎn)運體的高親和力抑制劑，抑制人源URAT1的轉(zhuǎn)運活性，IC50為25 nM。它抑制URAT1相關(guān)同源體OAT4和OAT1的IC50分別為5.9 μM和4.6 μM，相較于URAT1，親和力低

• 靶點： URAT1 transporter(Cell-free assay):25 nM;OAT

• 體外研究：
  Verinurad以濃度依賴性方式抑制人源URAT1的轉(zhuǎn)運活性，IC50為25 nM。Verinurad還抑制URAT1相關(guān)同系物OAT4和OAT1，IC50分別為5.9 μM和4.6 μM，親和力較之與URAT低200倍。Verinurad對人源URAT1比對大鼠URAT1的親和力高1640倍（human URAT1 IC50=0.025 μM，rat URAT IC50=41 μM）。Verinurad對人源URAT1具有高效力，URAT1的第35、365和481位殘基有助于verinurad結(jié)合。在人源URAT1在365位引入一個嵌合點突變（人源365位苯丙氨酸替換成大鼠365位的酪氨酸；h-F365Y），verinurad對其IC50為4 μM，比對野生型人源URAT1D低160倍。同時，如果在輸入URAT1引入類似的點突變（即將大鼠365位酪氨酸突變?yōu)槿嗽?65位的苯丙氨酸；r-Y365F），verinurad對其IC50為2.9 μM，比對野生型大鼠URAT1高14倍

• 體內(nèi)研究：
  在人體中，Verinurad單藥給藥吸收很快，其暴露量（Cmax和AUC）隨劑量的升高而升高。在饑餓狀態(tài)下，給藥0.5-0.75小時后達到Cmax；在進食狀態(tài)下，給藥后1.25小時達到Cmax。在不同劑量下，t1/2約為10-15小時。Verinurad在體內(nèi)耐受性良好。在體循環(huán)中，verinurad具有高清除率（CL/F ranged ~30-50 L/h），廣泛分布在血管外。其腎排泄率低，在尿液中僅2%-3%。大部分verinurad可能在肝臟中通過生物轉(zhuǎn)化形成代謝物

• 細胞實驗： Cell lines: HEK-293T細胞 Concentrations: 0.1 nM-1 mM Incubation Time: 5 min Method: URAT1 and OAT4 activity assays were performed in assay buffer con- sisting of 25 mM MES pH 5.5 (from a 1 M MES solution adjusted to pH 5.5 with sodium hydroxide), 125 mM sodium gluconate, 4.8 mM potassium gluconate, 1.2 mM monobasic potassium phosphate, 1.2 mM magnesium sulfate, 1.3 mM calcium gluconate and 5.6 mM glucose. URAT1 inhibitors were serially diluted into assay buffer and added to the cells for 5 minutes prior to addition of substrate. URAT1-expressing cells were incubated with 100 μM 14C-uric acid for 10 minutes and OAT4-expressing cells were incubated with 20 μM carboxyfluorescein for 5 minutes. Cells were then washed three times in 25 mM MES pH 5.5/125 mM sodium gluconate, and solubilized in Ultima Gold prior to liquid scintillation counting. Each treatment is measured in triplicate.

• 參考文獻：
  1. Philip K. Tan, et al. Discovery and characterization of verinurad, a potent and specific inhibitor of URAT1 for the treatment of hyperuricemia and gout. Scientific Reports. 2017, 7, Article number: 665. 2. Zancong Shen, et al. Pharmacokinetics, pharmacodynamics, and tolerability of verinurad, a selective uric acid reabsorption inhibitor, in healthy adult male subjects. Drug Des Devel Ther. 2017, 11: 2077–2086.

• 溶解性： Soluble  in  DMSO

• 保存條件： -20℃

• 配置溶液濃度參考：
  

  	1mg	5mg	10mg
  1 mM	2.87 ml	14.351 ml	28.701 ml
  5 mM	0.574 ml	2.87 ml	5.74 ml
  10 mM	0.287 ml	1.435 ml	2.87 ml
  50 mM	0.057 ml	0.287 ml	0.574 ml

• 注意：部分產(chǎn)品我司僅能提供部分信息，我司不保證所提供信息的權(quán)威性，僅供客戶參考交流研究之用。

輸入產(chǎn)品批號：

本計算器可幫助您計算出特定溶液中溶質(zhì)的質(zhì)量、溶液濃度和體積之間的關(guān)系，公式為：

質(zhì)量 (mg) = 濃度 (mM) x 體積 (mL) x 分子摩爾量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *