| 名稱 | Aprepitant |
| 描述 | Aprepitant is a Substance P/Neurokinin-1 Receptor Antagonist. The mechanism of action of aprepitant is as a Neurokinin 1 Antagonist, and Cytochrome P450 3A4 Inhibitor, and Cytochrome P450 2C9 Inducer, and Cytochrome P450 3A4 Inducer. |
| 細(xì)胞實(shí)驗(yàn) | Aprepitant is dissolved in DMSO. The inhibitory effect of aprepitant on metabolic activity of Nalm-6 cells is assessed by uptake of thiazolyl blue tetrazolium bromide (MTT) by viable cells. Cells are plated onto 96-well plates at a density of 5000 cells/well. After treatment with aprepitant at 5, 10, 15, 20 and 30 μM for 24, 36 and 48 h, the cells are further incubated with 100 μL of MTT (0.5 mg/mL) at 37°C for 3 h. Untreated cells are defined as the control group. Following solubilization of precipitated formazan with 100 μL of DMSO, the optical densitometry is measured with an ELISA reader at a wavelength of 578 nm. |
| 體外活性 | 在疼痛沖動(dòng)從外周受體到CNS 的傳感中,Aprepitant起關(guān)鍵作用,并參與對(duì)壓力的各種行為及神經(jīng)化學(xué)和心血管的反應(yīng).Aprepitant可穿透血腦屏障并與大腦中NK-1受體結(jié)合.Aprepitant可抑制化療引起的細(xì)胞毒性,如順鉑（阻斷P物質(zhì)）誘發(fā)的急性和延遲性嘔吐.Aprepitant（3 mg/kg,i.v.或p.o.）可抑制順鉑（10 mg/kg,i.v.）引起的嘔吐.Aprepitant（0.1 mg/kg,i.v.）與地塞米松（20 mg/kg,i.v.）或5–HT3 受體拮抗劑恩丹西酮（0.1 mg/kg,i.v.）聯(lián)用可加強(qiáng)止吐效果.在雪貂急性遲緩性嘔吐模型中,順鉑（5 mg/kg,i.p.）給藥后惡心并嘔吐的回應(yīng)記錄為72 h.Aprepitant（4-16 mg/kg,p.o.）預(yù)處理可劑量依賴性地抑制順鉑引起的嘔吐.Aprepitant（2-4 mg/kg/day,p.o.）完全抑制了所有給藥雪貂的惡心和嘔吐癥狀.通過(guò)注射順鉑24 h后可形成嘔吐急性期,開(kāi)始每天給藥,順鉑注射后 24 和48 h,Aprepitant（4 mg/kg,p.o.） 抑制了75%雪貂的惡心和嘔吐癥狀. |
| 體內(nèi)活性 | Aprepitant對(duì)人NK1受體的選擇性是人NK3受體的3000倍,比人NK2受體多出50,000倍。在使用人類和動(dòng)物組織(IC50> 3 μM)進(jìn)行的單胺攝取位點(diǎn)(NE, 5–HT, DA)計(jì)數(shù)篩選中,以及在人類單胺氧化酶A和B試驗(yàn)以及人類血清素5–HT1A, 5–HT2A, 5–HT2c, 5–HT3, 5–HT5, 5–HT6,和5–HT7 受體(IC50>3 μM)中,Aprepitant均是無(wú)活性的。Aprepitant與CNS和外周的NK-1受體結(jié)合而拮抗P物質(zhì)。CHO或 COS 細(xì)胞中hNK1受體上50%的P物質(zhì)會(huì)被Aprepitant（0.1 nM）取代。在放射性配體結(jié)合試驗(yàn)中,在放射性配體結(jié)合篩選的PANLABS 板中,采用原生動(dòng)物組織,Aprepitant抑制大鼠頜下腺中[3H]P物質(zhì)與天然NK1受體結(jié)合；經(jīng)檢查PANLABS篩選,Aprepitant與其他任何原生動(dòng)物G蛋白耦合的受體或離子通道均無(wú)明顯的相互作用。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : 12 mg/mL (22.5 mM)
DMSO : 18.33 mg/mL (34.3 mM)
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| 關(guān)鍵字 | Antibiotic | Human immunodeficiency virus | Bacterial | Tachykinin receptor | L754030 | Neurokinin Receptor | HIV | L 754030 | Inhibitor | MK 0869 | NK receptor | inhibit | Aprepitant | MK 869 | MK869 | MK0869 |
| 相關(guān)產(chǎn)品 | Dehydroacetic acid sodium | Emtricitabine | Doxycycline | Methyl anthranilate | Neomycin sulfate | Lamivudine | Dimethyl sulfoxide | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | Ampicillin sodium | Sulfamethoxazole sodium | Kanamycin sulfate |
| 相關(guān)庫(kù) | 經(jīng)典已知活性庫(kù) | 抗病毒庫(kù) | GPCR靶點(diǎn)分子庫(kù) | 膜蛋白靶向化合物庫(kù) | 神經(jīng)退行性疾病化合物庫(kù) | 抗癌臨床化合物庫(kù) | 抗癌藥物庫(kù) |