IC50: 5.7 μM (PCSK9)[1]
PCSK9-IN-11 (compound 5r) is a potent and orally active PCSK9 inhibitor. PCSK9-IN-11 exhibits PCSK9 transcriptional inhibitory activity in HepG2 cells, with an IC50 of 5.7 μM. PCSK9-IN-11 increases LDL receptor (LDLR) protein level. PCSK9-IN-11 can be used for atherosclerosis research[1].
PCSK9-IN-11 (compound 5r) (0-25 μM, 24 h) 以剂量依赖性方式显着降低 PCSK9 蛋白水平并增加 LDLR 表达[1]。
Western Blot Analysis[1]
| Cell Line: | HepG2 cells |
| Concentration: | 0, 2.5, 5, 12.5, 25 μM |
| Incubation Time: | 24 h |
| Result: | Significantly decreased PCSK9 protein level in a dose dependent manner. Markedly increased LDLR expression in a dose dependent manner. Significantly and dose-dependently increased DiI-LDL uptake by around 1.7 folds. |
PCSK9-IN-11 (compound 5r) (0-1000 mg/kg，灌胃，once) 具有更好的体内安全特性，半致死剂量 (LD50) 值超过 1000 mg/kg [1]。
PCSK9-IN-11 (30 mg/kg，灌胃，每天一次，持续 8 周) 显著抑制肝脏 PCSK9 表达并略微降低血清 PCSK9 水平[1]。
| Animal Model: | C57BL/6J mice[1] |
| Dosage: | 0, 250, 500 or 1000 mg/kg |
| Administration: | Intragastrically administrated, single dose |
| Result: | Exhibited a good in vivo safety feature with the halflethal dose (LD50) value of over 1000 mg/kg. Did not affected the body weight, behavioral and survival characteristics of mice. |
| Animal Model: | ApoE KO mice (under high-fat diet (HFD))[1] |
| Dosage: | 30 mg/kg |
| Administration: | Intragastric administration, once a day for 8 weeks |
| Result: | Significantly suppressed hepatic PCSK9 expression and slightly reduced serum PCSK9 level. |
[1]. Qiao MQ, et al. Structure-activity relationship and biological evaluation of xanthine derivatives as PCSK9 inhibitors for the treatment of atherosclerosis. Eur J Med Chem. 2022 Dec 26;247:115047.