ASP7657
目录号 : GC46088
An EP4 receptor antagonist
Cas No.:1196045-28-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
ASP7657 is an antagonist of the prostaglandin E2 (PGE2) receptor subtype EP4 (Kis = 2.21 and 6.02 nM for the human and rat receptors, respectively).1 It is selective for these receptors over the rat EP1, EP2, and EP3 receptors (IC50s = >1,000 nM for all), as well as a panel of 42 additional receptors and ion channels (IC50s = >1,000 nM for all). ASP7657 inhibits increases in cAMP accumulation induced by PGE2 in Jurkat cells expressing human EP4 and CHO cells expressing the rat receptor with IC50 values of 0.29 and 0.86 nM, respectively. It inhibits PGE2-induced decreases in LPS-stimulated TNF-α release in isolated rat whole blood in a dose-dependent manner. AP7657 (0.01 and 0.1 mg/kg per day) decreases albuminuria in the db/db mouse model of type 2 diabetes.
|1. Mizukami, K., Kamada, H., Yoshida, H., et al. Pharmacological properties of ASP7657, a novel, potent, and selective prostaglandin EP4 receptor antagonist. Naunyn Schmiedebergs Arch. Pharmacol. 391(12), 1319-1326 (2018).
| Cas No. | 1196045-28-9 | SDF | |
| Canonical SMILES | OC([C@H]1CC[C@H](CNC(C2=C(N(CC3=NC(C=CC=C4)=C4C=C3)C=C5)C5=CC(C(F)(F)F)=C2)=O)CC1)=O | ||
| 分子式 | C28H26F3N3O3 | 分子量 | 509.5 |
| 溶解度 | DMF: 16.5mg/mL,DMSO: 16.5mg/mL,DMSO:PBS (pH 7.2) (1:3): 0.25mg/mL,Ethanol: 12.5mg/mL | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9627 mL | 9.8135 mL | 19.6271 mL |
| 5 mM | 0.3925 mL | 1.9627 mL | 3.9254 mL |
| 10 mM | 0.1963 mL | 0.9814 mL | 1.9627 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Pharmacological properties of ASP7657, a novel, potent, and selective prostaglandin EP4 receptor antagonist
Naunyn Schmiedebergs Arch Pharmacol 2018 Dec;391(12):1319-1326.PMID:30076448DOI:10.1007/s00210-018-1545-x.
We determined the pharmacologic profile of ASP7657, trans-4-[({[1-(quinolin-2-ylmethyl)-5-(trifluoromethyl)-1H-indol-7 yl] carbonyl} amino) methyl] cyclohexanecarboxylic acid methanesulfonate (1:1), a newly synthesized selective E-type prostaglandin (EP)4 receptor antagonist using several in vitro and in vivo experiments. ASP7657 exhibited high affinity for rat and human EP4 receptors, with Ki values of 6.02 nM and 2.21 nM, respectively. In addition, ASP7657 potently inhibited the PGE2-induced cyclic adenosine monophosphate (cAMP) increase in Chinese hamster ovary (CHO) cells expressing rat EP4 receptors and human lymphoblastoid T (Jurkat) cells, with IC50 values of 0.86 nM and 0.29 nM, respectively. In contrast, ASP7657 did not inhibit the PGE2-induced intracellular calcium increase in HEK293 cells expressing rat EP1 and EP3 receptors, or cAMP increase in CHO cells expressing rat EP2 receptors. ASP7657 showed good pharmacokinetic properties following oral dosing and dose-dependently antagonized the prostaglandin (PG)E2-mediated inhibition of lipopolysaccharide-induced tumor necrosis factor-α release from rat whole blood culture. In addition, 4 weeks repeated oral administration of ASP7657 dose-dependently attenuated albuminuria in type 2 diabetic mice; these effects were significant at doses of 0.01 mg/kg or higher. These results demonstrate that ASP7657 is a potent and selective EP4 receptor antagonist that may be useful in future studies to help clarify the physiological and pathophysiological roles of PG.
Renoprotective effects of the novel prostaglandin EP4 receptor-selective antagonist ASP7657 in 5/6 nephrectomized chronic kidney disease rats
Naunyn Schmiedebergs Arch Pharmacol 2019 Apr;392(4):451-459.PMID:30554341DOI:10.1007/s00210-018-01600-3.
Prostaglandins (PGs) are important lipid mediators of numerous physiologic and pathophysiologic processes in the kidney. PGE2, the most abundant renal PG, plays a major role in renal physiology, including renin release and glomerular hemodynamics. We investigated the renoprotective properties of the novel PGE2 EP4 receptor-selective antagonist ASP7657 in 5/6 nephrectomized rats, a chronic kidney disease (CKD) model. Eight weeks of repeated administration of ASP7657 (0.001-0.1 mg/kg) dose-dependently and significantly reduced urinary protein excretion and attenuated the development of glomerulosclerosis and tubulointerstitial damage, including fibrosis and inflammatory cell infiltration, without affecting blood pressure. Additionally, ASP7657 tended to have beneficial effects on renal function, as indicated by the decrease in plasma creatinine and blood urea nitrogen levels and attenuation of the decline in creatinine clearance (Ccr). The angiotensin II receptor blocker losartan (10 mg/kg) also showed these renoprotective effects while significantly reducing blood pressure. ASP7657 dose-dependently and significantly reduced the EP4 receptor agonist-induced increase in plasma renin activity, as assessed by angiotensin I release in normal rats. Additionally, ASP7657 attenuated hyperfiltration assessed by Ccr without changing the renal blood flow or blood pressure in diabetic rats. These results suggest that ASP7657 suppresses the progression of chronic renal failure by modulating renin release and improving renal hemodynamics, and may therefore be a promising therapeutic option for inhibiting the progression of CKD.