| 产品描述： | MK-0354 is a partial agonist of GPR109a receptor, for hGPR109a/ mGPR109a with EC50 of 1.65/1.08 μM, showed no activation of GPR109b. IC50 value: 1.65 μM (EC50, for hGPR109a), 1.08 μM (EC50, for mGPR109a) [1] Target: GPR109a in vitro: MK-0354 demonstrated clear and statistically significant partial agonism in the cAMP assays for both the mouse and human receptors with efficacy approximately 60-70% of that of either nicotinic acid or β-hydroxy butyrate, a putative physiologically relevant ligand for hGPR109a, in the same assay platform. In addition, MK-0354 showed no activation of GPR109b in the cAMP assay at any concentration up to 100 μM. Following these interesting observations, we then prepared a number of other 5,5-fused pyrazoles analogous to those that showed receptor activity in our earlier studies. MK-0354 appeared to be somewhat unique among the members of the pyrazole tetrazole series in having reasonable receptor activity. in vivo: MK-0354 retained the plasma free fatty acid lowering effects in mice associated with GPR109a agonism, but did not induce vasodilation at the maximum feasible dose. Moreover, preadministration of MK-0354 blocked the flushing effect induced by nicotinic acid but not that induced by PGD2. This profile made MK-0354 a suitable candidate for further study for the treatment of dyslipidemia. MK-0354 is a GPR109A partial agonist that activates the antilipolytic pathway in adipocytes. The single-dose and multiple-dose pharmacokinetics and pharmacodynamics, as well as tolerability, of MK-0354 were examined in two Phase I studies conducted in healthy male volunteers. The lipid efficacy of MK-0354 was assessed in a Phase II study conducted in male and female patients with dyslipidemia. |
| 靶点： |
GPR109A |
| 体内研究： |
MK-0354 (50 mg/kg；腹腔注射；每日一次；在肿瘤植入前 7 天给药并持续至实验结束) 未能抑制携带 Hepa1-6 肿瘤的 C57BL/6 小鼠肿瘤生长或改变免疫细胞浸润。 |
| 参考文献： |
1. Semple G, et al. 3-(1H-Tetrazol-5-yl)-1,4,5,6-tetrahydro-cyclopentapyrazole (MK-0354): A Partial Agonist of the Nicotinic Acid Receptor, G-Protein Coupled Receptor 109a, with Antilipolytic but No Vasodilatory Activity in Mice. J. Med. Chem., 2008, 51 (16) 2. Lai E1, et al. Effects of a niacin receptor partial agonist, MK-0354, on plasma free fatty acids, lipids, and cutaneous flushing in humans. J Clin Lipidol. 2008 Oct;2(5):375-383. |
| 溶解性： |
Soluble in DMSO |
| 保存条件： |
-80℃（运输条件：冰袋低温运输） |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
5.676 ml |
28.38 ml |
56.761 ml |
| 5 mM |
1.135 ml |
5.676 ml |
11.352 ml |
| 10 mM |
0.568 ml |
2.838 ml |
5.676 ml |
| 50 mM |
0.114 ml |
0.568 ml |
1.135 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京