Torcetrapib

製品コードS2792 バッチS279250

印刷

化学情報

Chemical Structure Synonyms CP-529414 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C26H25F9N2O4
分子量 600.47 CAS No. 262352-17-0
Solubility (25°C)* 体外 DMSO 120 mg/mL (199.84 mM)
Ethanol 6 mg/mL (9.99 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Torcetrapib (CP-529414) is a CETP inhibitor with IC50 of 37 nM, elevates HDL-C and reduces nonHDL-C in plasma. Phase 3.
in vitro Torcetrapib dose-dependently increases aldosterone release from H295R cells after either 24 or 48 h of treatment with an EC50 of approximately 80 nM, this effect is mediated by calcium channel as calcium channel blockers completely blocks torcetrapib-induced corticoid release and calcium increase. Torcetrapib (1 μM) significantly increases the expression of steroidogenic gene, CYP11B2 and CYP11B1, in H295R cell lines. [2]
in vivo Torcetrapib (< 100 mg, daily) changes the plasma distribution of CETP, as the apparent molecular weight of the CETP has shifted to a larger form, by 2 hours after the dose in healthy young subjects. Torcetrapib treatment with 10 mg, 30 mg, 60 mg, and 120 mg daily and 120 mg twice daily results in 16%, 28%, 62%, 73%, and 91% increases in plasma HDL-C, respectively, with no significant changes in TPC in healthy young subjects. [1] Torcetrapib results in an increase of 72.1% in high-density lipoprotein cholesterol and a decrease of 24.9% in low-density lipoprotein cholesterol, in addition to an increase of 5.4 mm Hg in systolic blood pressure, a decrease in serum potassium, and increases in serum sodium, bicarbonate, and aldosterone, in patients at high cardiovascular risk after 12 months' treatment. [3] Torcetrapib increases HDL cholesterol levels by 50% and 60% at dose of 60 mg daily and 120 mg daily, respectively, in both healthy and moderately hyperlipidemic subjects. Torcetrapib 60 mg daily increases HDL-mediated net cholesterol efflux from foam cells primarily by increasing HDL concentrations, whereas 120 mg daily torcetrapib increases cholesterol efflux both by increasing HDL concentration and by causing increased efflux at matched HDL concentrations. [4] Torcetrapib (90 mg/kg/day) results in a 70% inhibition of CE transfer in rabbits fed an atherogenic diet. Torcetrapib (90 mg/kg/day) increases mean HDL-C levels by above 3-fold and apoA-I levels by 2.5-fold in plasma in rabbits fed an atherogenic diet. Torcetrapib-treated animal has a multiple-fold increase in HDL-C AUC and a corresponding reduction in aortic lesion area with 60% reduction of aortic free cholesterol (FC) and cholesteryl ester (EC) in rabbits fed an atherogenic diet. Torcetrapib-treated rabbits stimulate free cholesterol efflux to a significantly greater extent than does sera from control rabbits. [5]

プロトコル(参考用のみ)

キナーゼアッセイ Assay of CETP Activity
For determination of plasma CETP activity, transfer of 3H-CO from HDL to the nonHDL plasma fraction and from 14C-CO-labeled LDL to HDL are determined simultaneously. For in vitro assay, tracer levels of 3H-HDL and 14C-LDL are added to plasma and the samples incubated for 1.5, 2.25, and 3 hours in quadruplicate; after which, the nonHDL fraction is precipitated by adding an equal volume of 20% (wt/vol) PEG8000, and radioactivity in the HDL containing supernatant is determined by scintillation counting. The fraction of CE transferred is calculated from the loss of 3H- and 14C-radioactivity from the HDL and nonHDL fractions, respectively, relative to the non-incubated zero time sample, by the method of Pattnaik based on first-order isotope kinetics. To determine if the single exponential decay function is sufficient for calculating relative inhibition, plasma and HDL free and total cholesterol are measured and CE is calculated by subtracting free from total. This allowed the actual specific activity of 3H-HDL-CE and 14C-nonHDL-CE at each time point to be determined, and it therefore eliminated error caused by dissolution of specific activity through exchange. In this case, the decay rate for label divided by the specific activity produced the transfer rate (nmol/h) that, on integration, gives the nmol of CE transferred per time period. The percent inhibition, relative to control, is calculated using data for the linear portion of the transfer curve. The near equivalence of demonstrated that for the purposes of the clinical trial, the former method would be sufficient.
動物実験 動物モデル Male New Zealand White rabbits feed with an atherogenic diet
投薬量 90 mg/kg/day
投与方法 Dietary feeding

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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