| 名稱 | Stiripentol |
| 描述 | Stiripentol (BCX2600) (STP) is an anticonvulsant agent, which can inhibit N-demethylation of CLB to NCLB mediated by CYP3A4 (noncompetitively) and CYP2C19 (competitively) with Ki of 1.59/0.516 μM and IC50 of 1.58/3.29 μM, respectively. |
| 細(xì)胞實(shí)驗(yàn) | The inhibition constants (apparent Ki) of Stiripentol (STP) for CLB demethylation by CYP3A4 and CYP2C19 are determined using various concentrations of CLB (2, 10, 20, 40, 60, and 100 μM) with increasing concentrations of Stiripentol (STP) (0, 0.5, 1, 2, and 5 μM). Concerning NCLB hydroxylation by CYP2C19, the apparent Ki is similarly determined with different concentrations of NCLB (1.5, 4, 6, 8, 12, and 14 μM) and STP (0, 0.1, 0.5, 1, and 2 μM). IC50 values are determined by coincubation of the substrate at the concentration in the range of the therapeutic plasma concentrations (2 μM CLB or 14 μM NCLB) with increasing concentrations of Stiripentol (STP) (0.001-10 μM) [1]. |
| 動(dòng)物實(shí)驗(yàn) | Two age groups, p1M (n=18, age 4 weeks) and p5M (n=18, age 5-10 months), of Scn1aRX/+ mice are assigned in this experiment. Both groups are divided randomly into three subgroups (n=6), and each subgroup is administered Stiripentol (STP) (300 mg/kg) alone, CLB (6.62 mg/kg) alone, or a combination of Stiripentol (STP) (p1M; 150 mg/kg, p5M; 300 mg/kg) and CLB (6.62 mg/kg). All drugs are administered by intraperitoneal injection (i.p.) after a 48-h recovery from baseline seizure study. Blood samples are collected at 1 h and 20 min after administration of CLB or STP+CLB for measurement of plasma concentrations of CLB and N-desmethylclobazam, respectively [2]. |
| 體外活性 | Stiripentol (STP) 抑制CLB去甲基化的活性，對(duì)于cDNA表達(dá)的CYP3A4而言，其抑制效果通過(guò)非競(jìng)爭(zhēng)性抑制模型最佳描述，表觀Ki值為1.6 μM；而對(duì)于cDNA表達(dá)的CYP2C19，則通過(guò)競(jìng)爭(zhēng)性抑制模型描述更為恰當(dāng)，Ki值為0.52 μM。此外，Stiripentol (STP) 以競(jìng)爭(zhēng)性抑制的方式，抑制cDNA表達(dá)的CYP2C19將NCLB轉(zhuǎn)化為OH-NCLB，Ki值為0.14 μM [1]。 |
| 體內(nèi)活性 | 在對(duì)小鼠進(jìn)行單一使用Stiripentol（STP）治療時(shí)，其基礎(chǔ)體溫1（BT1，39.67±1.09°C）與基礎(chǔ)體溫2（BT2，41.32±1.05°C）之間的差異達(dá)到了統(tǒng)計(jì)學(xué)顯著性（t=3.097, p<0.05）。Stiripentol（STP）單療與CLB單療間的BT2差異亦具有統(tǒng)計(jì)學(xué)意義（t=2.615, p<0.05）。在采用Stiripentol（STP）加CLB聯(lián)合治療的小鼠中，BT1（40.18±0.58°C）與BT2（43.03±0.49°C）之間的差異顯著（t=10.44, p<0.01）[2]。 |
| 存儲(chǔ)條件 | store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 55 mg/mL (234.75 mM)
Ethanol : 30 mg/mL
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| 關(guān)鍵字 | Stiripentol | Inhibitor | inhibit | BCX 2600 | CYPs | BCX-2600 | Cytochrome P450 |
| 相關(guān)產(chǎn)品 | Naringin | 1-Aminobenzotriazole | Gemfibrozil | Fenofibrate | Tauroursodeoxycholate | Methoxsalen | Doxepin hydrochloride | Naringenin | Apigenin | 1-Ethynylnaphthalene | Tebuconazole | Diflubenzuron |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 抗癌上市藥物庫(kù) | 經(jīng)典已知活性庫(kù) | 已知活性化合物庫(kù) | EMA 上市藥物庫(kù) | 抗衰老化合物庫(kù) | FDA 上市藥物庫(kù) | 藥物功能重定位化合物庫(kù) | 抗癌臨床化合物庫(kù) | 抗癌藥物庫(kù) |