URAT1 inhibitor 2 是一种口服有效的URAT1和CYP isozyme抑制剂，对 URAT1 介导的14C-UA 吸收、CYP1A2、CYP2C9 的IC50分别为 1.36 μM、16.97 μM、5.22 μM。URAT1 inhibitor 2 在高尿酸血症和痛风的研究中是一个有前途的候选药物。
| 生物活性 | URAT1 inhibitor2 is an orally active and potentURAT1andCYP isozymeinhibitor, withIC50values of 1.36 μM, 16.97 μM, 5.22 μM for URAT1-mediated14C-UA uptake, CYP1A2 and CYP2C9, respectively.URAT1 inhibitor2 is a promising drug candidate in the study of hyperuricemia and gout[1]. |
| IC50& Target | IC50: 1.36 μM (URAT1-mediated14C-UA uptake), 16.97 μM (CYP1A2), 5.22 μM (CYP2C9), >20 μM (CYP2C19), >20 μM (CYP2D6), and >20 μM (CYP3A4M)[1]. |
体外研究
(In Vitro) | URAT1 inhibitor 2 (compound 23) (0-50 μM, 3-20 min) inhibits URAT1-mediated14C-UA uptake (IC50= 1.36 μM) and CYP cells activity[1].
Cell Viability Assay | Cell Line: | Human URAT1, CYP cells[1] | | Concentration: | 0, 0.05, 0.15, 0.5, 1.5, 5.0, 15, and 50 μM | | Incubation Time: | 3-20 min | | Result: | Inhibited URAT1-mediated 14C-UA uptake and CYP cells activity. |
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体内研究
(In Vivo) | URAT1 inhibitor 2 (Intravenous at 2 mg/kg or orally at 10 mg/kg) has excellent pharmacokinetic properties with the oral bioavailability of 59.3%[1].
URAT1 inhibitor 2 (4, 2, 1, 0.5, and 0.25 mg/kg; Orally) shows orally active and outstanding SUA-lowering activity with a dose-dependent manner in acute hyperuricemia mice[1].
URAT1 inhibitor 2 (1000 mg/kg, intragastric administration, once) shows favorable safety profiles and no obvious acute toxicity[1].
Pharmacokinetic Parameters of URAT1 inhibitor 2 in male Sprague-Dawley rats[1].
| parameter | unit | p.o. | i.v. | | compoundmax(h) | | 23 | 23 | | AUC (0-t) | ng/mL·h | 48754.6 | 16344.8 | | AUC (0-∞) | ng/mL·h | 48781.5 | 16448.8 | | MRT (0-∞) | h | 3.3 | 1.0 | | t1/2 | h | 2.2 | 1.8 | | Tmax | h | 0.3 | | | Cmax | ng/mL | 19185.0 | | | CL | mL/min/kg | | 2.2 | | F | % | 59.3 | |
| Animal Model: | Male Sprague-Dawley rats (n=10)[1] | | Dosage: | 2 mg/kg (intravenous) or 10 mg/kg (oral administration) | | Administration: | Intravenous or oral administration | | Result: | Achieved excellent pharmacokinetic properties with the oral bioavailability of 59.3%. |
| Animal Model: | Acute hyperuricemia mice[1] | | Dosage: | 4, 2, 1, 0.5, and 0.25 mg/kg | | Administration: | Orally, once | | Result: | Showed outstanding SUA-lowering activity. |
| Animal Model: | Kunming mice[1] | | Dosage: | 1000 mg/kg | | Administration: | Itragastric administration, once | | Result: | Showed favorable safety profiles and no obvious acute toxicity. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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