[ 鐧诲綍] [ 鍏嶈垂娉ㄥ唽]
璇曞墏浠櫒缃? title=
浣嶇疆锛欬a href="/">棣栭〉> 浜у搧搴掽/a> > Orteronel(racemic)
绔嬪嵆鍜ㄨ
鍜ㄨ绫诲瀷锛欬/div>
*濮撳悕锛欬/div>
*鐢佃瘽锛欬/div>
*鍗曚綅锛欬/div>
Email锛欬/div>
*鐣欒█鍐呭锛欬/div>
璇疯缁嗚鏄庢偍鐨勯渶姹傘€
*楠岃瘉鐮侊細
Orteronel(racemic)
鏈骇鍝佷笉鍚戜釜浜洪攢鍞紝浠呯敤浣滅瀛︾爺绌讹紝涓嶇敤浜庝换浣曚汉浣撳疄楠屽強闈炵鐮旀€ц川鐨勫姩鐗╁疄楠屻€侟/div>
Orteronel(racemic)鍥剧墖
CAS NO: 426219-18-3
瑙勬牸: 鈮?8%
鍖呰涓庝环鏍硷細
鍖呰 浠锋牸(鍏?
5mg 鐢佃
10mg 鐢佃
25mg 鐢佃
50mg 鐢佃
100mg 鐢佃
250mg 鐢佃
500mg 鐢佃

浜у搧浠嬬粛
鐞嗗寲鎬ц川鍜屽偍瀛樻潯浠迭/div>
Molecular Weight (MW) 307.35
Formula C18H17N3O2
CAS No. 566939-85-3 (s-isomer); 426219-18-3 (racemic)
Storage -20鈩 for 3 years in powder form
-80鈩 for 2 years in solvent
Solubility (In vitro) DMSO: 61 mg/mL (198.5 mM)
Water:<1 mg/mL
Ethanol: 8 mg/mL (26.0 mM)
Solubility (In vivo) 0.5% methylcellulose: 30 mg/mL
Synonyms TAK700; TAK-700; TAK 700 racemate
瀹為獙鍙傝€冩柟娉旤/div>
In Vitro

In vitro activity: In vitro, TAK-700 shows the potent inhibitory activity against rat and human steroid 17,20-lyase with IC50 of 54 nM and 38 nM, respectively. While other CYP isoforms including 11-hydroxylase and CYP3A4 are not significantly affected by TAK-700. In microsomes expressing human CYP isoforms, TAK-700 exhibit greater inhibitory effects on 17,20-lyase with IC50 of 19 nM compared to the other CYP isoforms. TAK-700 shows the inhibitory activity against monkey 17,20-lyase and 17-hydroxylase with IC50 of 27 nM and 38 nM, respectively. In monkey adrenal cells, TAK-700 inhibits the ACTH stimulated production of DHEA and androstenedione with IC50 of 110 nM and 130 nM, respectively. Moreover, TAK-700 also potently inhibits DHEA production in human adrenocortical tumor line H295R cells with IC50 of 37 nM.


Kinase Assay: Rat 11-hydroxylase activity is measured according to a method described for side-chain cleavage activity previously with some modifications. The reaction mixture contained 200 mM mannitol, 4.5 mM HEPES, 2.3 mM potassium phosphate (pH 7.4), 0.1 mM EDTA路2 K, 0.03% BSA (crystallized), 4.5 mM NADPH, 11 mM calcium chloride, 4 渭g of mitochondria protein, 10 nM [1,2-3H]-hydroxy-11-deoxycorticosterone (11-deoxycortisol) (NEN, dissolved in 0.02% Tween-80), and 1-1000 nM test compounds in a total volume of 150 渭L. The concentrations of reagents are expressed as the final concentration in the reaction mixture. The test compounds are serially diluted with dimethylformamide, and 1.5 渭L is added directly to the reaction mixture. After 30 min incubation at 37掳C the reaction is terminated by addition of 400 渭L of ethyl acetate and 100 渭L of distilled water, then vortexed for 30 s and briefly centrifuged. Three hundred 渭Ls of the organic phase is transferred to a new tube and evaporated until dry using nitrogen gas. The steroids are dissolved with 30 渭L of ethyl acetate and the whole volume is applied to silica gel TLC plates. The substrate and the products (11-deoxycortisol and cortisol) are separated in the toluene-acetone (7:2) solvent system.


Cell Assay: In monkey adrenal cells, orteronel inhibits the ACTH stimulated production of DHEA and androstenedione with IC50 of 110 nM and 130 nM, respectively. Moreover, Orteronel also potently inhibits DHEA production in human adrenocortical tumor line H295R cells with IC50 of 37 nM. In vitro, orteronel shows the potent inhibitory activity against rat and human steroid 17,20-lyase with IC50 of 54 nM and 38 nM, respectively. While other CYP isoforms including 11-hydroxylase and CYP3A4 are not significantly affected by Orteronel. In microsomes expressing human CYP isoforms, Orteronel exhibit greater inhibitory effects on 17,20-lyase with IC50 of 19 nM compared to the other CYP isoforms.

In Vivo In cynomolgus monkeys, oral treatment of TAK-700 at a dose of 1 mg/kg markedly reduces serum testosterone and dehydroepiandrosterone (DHEA) levels. Oral treatment of TAK-700 at a dose of 1 mg/kg results in favorable pharmacokinetic parameters with Tmax, Cmax, t1/2 and AUC0-24 hours of 1.7 hours, 0.147 渭g/mL, 3.8 hours and 0.727 渭g h/mL, respectively.
Animal model Adult male cynomolgus monkeys.
Formulation & Dosage Dissolved in 0.5% methylcellulose; 鈮? mg/kg; Oral gavage
References Bioorg Med Chem. 2011 Nov 1;19(21):6383-99; J Steroid Biochem Mol Biol. 2012 Apr;129(3-5):115-28.
Baidu
map