产品描述: Olodanrigan (EMA401, PD-126055, (S) PD-126055) 是一种高度选择性的、具有口服活性的外周限制性 angiotensin II type 2 receptor (AT2R) 拮抗剂。Olodanrigan 的镇痛作用可能涉及抑制增强 AngII/AT2R 诱导的 p38 和 p42/p44 MAPK 激活,从而抑制 DRG 神经元过度兴奋和 DRG 神经元的萌芽 |
靶点:
AT2R;RAAS |
体外研究:
EMA401 may act on paracrine/autocrine mechanisms at peripheral nerve terminals, or intracrine mechanisms, to reduce neuropathic pain signalling in AngII/NGF/TRPV1-convergent pathways |
体内研究:
EMA401, a selective small molecule antagonist of the AT2R, results in a significant attenuation of theta power and increase in paw withdrawal latencies (PWL) in rats at day 14 after chronic constriction injury (CCI). |
细胞实验:
Cell lines: rat DRG neurons Concentrations: 10, 100 nM Incubation Time: 30 min Method: 48 h after plating, duplicate dishes were treated with AngII (10 nM), AngII + EMA401 (10 and 100 nM respectively), 100 nM EMA401, NGF (100 ng/ml) or vehicle treated (control 0), for 30 min at 37 ℃, then fixed with 4% PFA for 30 min for immunostaining. |
动物实验:
Animal Models: Adult male Sprague-Dawley (SD) rats with a unilateral chronic constriction injury (CCI) of the sciatic nerve Dosages: 1 mg/kg (i.v.); 10 mg/kg (p.o.) Administration: i.v.; p.o. |
参考文献:
1. Anand U, et al. Mechanisms underlying clinical efficacy of Angiotensin II type 2 receptor (AT2R) antagonist EMA401 in neuropathic pain: clinical tissue and in vitro studies. Mol Pain. 2015 Jun 26;11:38. 2. Smith MT, et al.Small molecule angiotensin II type 2 receptor (AT₂R) antagonists as novel analgesics for neuropathic pain: comparative pharmacokinetics, radioligand binding, and efficacy in rats. Pain Med. 2013 May;14(5):692-705. |
溶解性:
DMSO: ≥ 34 mg/mL |
保存条件:
-20℃ |
配置溶液浓度参考:
|
1mg |
5mg |
10mg |
1 mM |
1.97 ml |
9.851 ml |
19.701 ml |
5 mM |
0.394 ml |
1.97 ml |
3.94 ml |
10 mM |
0.197 ml |
0.985 ml |
1.97 ml |
50 mM |
0.039 ml |
0.197 ml |
0.394 ml |
|
注意: |
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