JNJ-39933673

TA-1887(JNJ-39933673)是一种高效、选择性和口服活性SGLT2抑制剂(IC50:1.4nM),具有降血糖作用。TA-1887可用于糖尿病研究[1][2]。

研究领域 >> 代谢疾病

信号通路 >> 跨膜转运 >> SGLT

SGLT2:1.4 nM (IC50)

SGLT1:230 nM (IC50)

TA-1887(30 mg/kg,口服,大鼠)在每200 g体重2502 mg的24小时内诱导葡萄糖排泄[1]。TA-1887(3 mg/kg,口服)在不影响高血糖高脂肪饮食喂养的KK(HF-KK)小鼠的食物摄入量的情况下降低血糖水平[1]。TA-1887(30 mg/kg/天,口服灌胃2周)显著降低BSA负荷过重糖尿病小鼠的肾小球滤过率[2]。TA-1887(0.01%w/w,喂食含HF食物的小鼠)对抗糖尿病恶病质,并降低糖尿病小鼠的死亡率[3]。动物模型：Sprague-Dawley大鼠[1]剂量：30mg/kg给药：口服结果：通过持续抑制肾葡萄糖再摄取,诱导大范围UGE(尿糖排泄)。动物模型：BSA超载糖尿病小鼠[2]剂量：30 mg/kg给药：口服灌胃2周结果：抑制载体治疗的BSA超限糖尿病小鼠TGF-β2水平的诱导。抑制COL3基因水平。动物模型：雄性Sprague-Dawley大鼠(药代动力学分析)[1]剂量：3 mg/kg(静脉注射),10 mg/kg(口服)给药：口服(口服),静脉注射

[1]. Sumihiro Nomura, et al. Novel Indole-N-glucoside, TA-1887 As a Sodium Glucose Cotransporter 2 Inhibitor for Treatment of Type 2 Diabetes. ACS Med Chem Lett. 2013 Nov 13;5(1):51-5.

[2]. Keiji Shimada, et al. Adenosine/adenosine type 1 receptor signaling pathway did not play dominant roles on the influence of sodium-glucose cotransporter 2 inhibitor in the kidney of bovine serum albumin-overloaded streptozotocin-induced diabetic mice. J Diabetes Investig. 2022 Jun;13(6):955-964.

[3]. Taichi Sugizaki, et al. Treatment of diabetic mice with the SGLT2 inhibitor TA-1887 antagonizes diabetic cachexia and decreases mortality. NPJ Aging Mech Dis. 2017 Sep 8;3:12.