| 名稱 | LY334370 |
| 描述 | LY334370 is a selective 5-HT1F receptor agonist with a Ki of 1.6 nM |
| 細(xì)胞實驗 | For in vitro studies, LY334370 is dissolved in buffer solution.Human cerebral artery is used in this study. Segments are prepared as previously described, but briefly they are placed in a buffer solution containing (mM) NaCl 119, NaHCo3 15, KCl 4.6, CaCl2 1.5, NaH2PO4 1.2, MgCl2 1.2, and glucose 5.5. Sections of vessel about 0.5 mm in diameter and 1 to 2 mm in length are mounted in a temperature-controlled tissue bath (37°C) containing buffer solution bubbled with 95% O2 and 5% CO2. The vessel segments are given a tension of 4 mN and allowed to stabilize at this tension for 1 to 1.5 h. Vessel reactivity is tested by exposure to 60 mM KCl. This is done twice for each segment and only if the response is similar to the segment used for LY334370 testing. Responses to LY334370 is calculated as a percentage of the maximum KC1 response. |
| 激酶實驗 | AlphaScreen Assay: All reagents are diluted in 50 mM HEPES, 0.1% BSA, pH 7.5 supplemented with 0.01% Tween20 and allowed to equilibrate to room temperature prior to addition to plates. Catalytic turnover assays are run in 10 μL volumes in lowvolume 384-well plates at RT. The reaction consisted of enzyme (5 nM), biotinylated substrate peptide (30 nM), Fe(II) (1 μM), ascorbate (100 μM), 2OG (10 μM) and run at RT. For PHD2, the reaction consisted of enzyme (5 nM), biotinylated substrate peptide (60 nM), Fe(II) (20 μM), ascorbate (200 μM), 2OG (2 μM) and run at RT. EDTA is used to quench the reaction (5 μL), AlphaScreen donor (Streptavidin-conjugated) and acceptor (Protein A-conjugated) beads preincubated with peptide product antibodies are added (5 μL). Plates are foil-sealed to protect from light, incubated at room temperature for 60 minutes and read on a PHERAstar FS plate reader using an AlphaScreen 680 excitation/570 emission filter set. The final bead concentration in 20 μL reaction is 20 μg/mL. IC50 values are calculated in Prism 6 after normalisation against corresponding DMSO controls. |
| 動物實驗 | LY334370 is dissolved in 0.9% saline and is administered at a volume of 1 mL/kg. Male Sprague-Dawley rats (300 to 400 g) are treated with LY334370 (3 or 10 mg/kg, iv.). |
| 體外活性 | LY334370在體外對人腦動脈不表現(xiàn)出血管收縮效應(yīng)，直至劑量達(dá)到10^-5 M，此時可觸發(fā)8.5±5.7%的收縮率，但此結(jié)果并不顯著。 |
| 體內(nèi)活性 | 經(jīng)靜脈注射LY334370后，以3 mg/kg (n=3) 或10 mg/kg (n=6) 劑量進行電刺激，可以觀察到硬腦膜血管直徑分別增加至135±6%和106±11%，這與各自的對照值無顯著差異。LY334370本身對硬腦膜血管直徑無影響，因為在藥物注射前后15分鐘，硬腦膜血管的實際直徑分別為43±4任意單位和43±4任意單位（10 mg/kg）。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 50 mg/mL (142.28 mM), Sonication is recommended.
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| 關(guān)鍵字 | Serotonin Receptor | LY-334370 | LY334370 | Inhibitor | inhibit | 5-hydroxytryptamine Receptor | 5HTReceptor | 5-HT1F | 5-HT Receptor | 5HT Receptor |
| 相關(guān)產(chǎn)品 | Cinchonidine | D-Menthol | Cloperastine hydrochloride | Alverine citrate | Amitriptyline hydrochloride | Olanzapine | Dapoxetine hydrochloride | Trazodone hydrochloride | Mianserin hydrochloride | Fluoxetine hydrochloride | Serotonin hydrochloride | Clozapine N-Oxide |
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