| 名稱 | Anacetrapib |
| 描述 | Anacetrapib (MK-0859) (MK0859) is an effective, specific, reversible rhCETP and mutant CETP(C13S) inhibitor (IC50: 7.9 nM and 11.8 nM). Anacetrapib reduces the transfer of cholesteryl ester from HDL to LDL and/or VLDL thereby, producing an increase in serum HDL-cholesterol levels and a decrease in serum LDL-cholesterol levels. |
| 細(xì)胞實(shí)驗(yàn) | Anacetrapib (ANA) is dissolved in DMSO and diluted with appropriate media[2]. Cells are seeded in a 96 well plate overnight prior to the treatment by different concentrations of CETP inhibitors (e.g., Anacetrapib) for 24 h. Cell viability is measured using the CellTiter-Glo Luminescent Cell Viability Assay kit. Four wells are evaluated under each experimental condition[2]. |
| 激酶實(shí)驗(yàn) | The inhibitory potency (IC50) of Dalcetrapib, Torcetrapib, and Anacetrapib to decrease CE transfer from HDL to LDL by rhCETP and C13S CETP is measured using a scintillation proximity assay kit. Briefly, [3H]CE-labeled HDL donor particles are incubated in the presence of purified CETP proteins (final concentration 0.5 μg/mL) and biotinylated LDL acceptor particles for 3 h at 37°C. Subsequently, streptavidin-coupled polyvinyltoluene beads containing liquid scintillation cocktail binding selectively to biotinylated LDL are added, and the amount of [3H]CE molecules transferred to LDL is measured by β counting[1]. |
| 體外活性 | Anacetrapib對巨噬細(xì)胞膽固醇逆向轉(zhuǎn)運(yùn)有促進(jìn)作用,可增加30%的排泄物膽固醇含量.處理異常倉鼠模型,持續(xù)處理2周,與對照組相比,Anacetrapib （60 mg/kg/day）使CETP活性下降94%,HDL-膽固醇上升47%,不影響非HDL膽固醇濃度.與對照組相比,Anacetrapib處理的倉鼠HDL顯示ABCG1和SR-B1調(diào)節(jié)的流出物增多. [14C]Anacetrapib（10 mg/kg,p.o.）給藥48 h后,鼠和猴分別恢復(fù)～80和90%放射性,但排泄物中放射性幾乎無變化. |
| 體內(nèi)活性 | Anacetrapib和抑制素聯(lián)用時,既可提高HDL-膽固醇水平,也可降低LDL-膽固醇水平。Anacetrapib劑量依賴性地抑制CE從HDL3轉(zhuǎn)變?yōu)镠DL2。Anacetrapib對[14C]-dalcetrapibthiol與人類重組CETP的結(jié)合數(shù)無影響。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 50 mg/mL (78.43 mM), Sonication is recommended.
Ethanol : 57 mg/mL (89.41 mM), Sonication is recommended.
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| 關(guān)鍵字 | rhCETP | Mutant CETP (C13S) | MK0859 | MK 0859 | Inhibitor | inhibit | Cholesteryl ester transfer protein | CETP | Anacetrapib |
| 相關(guān)產(chǎn)品 | Granotapide | Dalcetrapib | Obicetrapib | Lomitapide Mesylate | KD-026 | Lomitapide | Torcetrapib | Implitapide | TAP311 | BMS-212122 | Evacetrapib | Dirlotapide |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 代謝化合物庫 | ReFRAME 相關(guān)化合物庫 | 活性脂質(zhì)化合物庫 | 含氟化合物庫 | 抗心血管疾病化合物庫 | 抗肥胖化合物庫 | 臨床期小分子藥物庫 | 藥物功能重定位化合物庫 | 抗代謝疾病化合物庫 |