Bumetanide (Synonyms: 布美她尼; Ro 10-6338; PF 1593)
Bumetanide (Ro 10-6338; PF 1593) 是一種高效的li尿劑，是 Na+-K+-Cl+ 協(xié)同轉(zhuǎn)運蛋白 (NKCC) 的阻斷劑。Bumetanide 是選擇性的 NKCC1 抑制劑，但對 NKCC2 也有抑制作用，對 hNKCC1A 和 hNKCC2A 作用的 IC50 值分別為 0.68 μM 和 4.0 μM。
生物活性
Bumetanide (Ro 10-6338; PF 1593), a highly potent loop diuretic, is a Na+-K+-Cl+ cotransporter (NKCC) blocker. Bumetanide is a selective NKCC1 inhibitor, but also inhibits NKCC2, with IC50s of 0.68 μM and 4.0 μM for hNKCC1A and hNKCC2A, respectively
IC50 & Target
IC50: 0.68 μM (hNKCC1A), 4.0 μM (hNKCC2A)[1]
體外研究(In Vitro)
Bumetanide has inhibitory effects for the two major human splice variants of NKCCs, hNKCC1A and hNKCC2A [1].
Bumetanide (0.03-100 μM; 5 minutes) inhibits the 86Rb+ uptake in NKCC1A-expressing oocytes in a dose-dependent manner[1].
Bumetanide inhibits NKCC2 isoform B in HEK-293 cells with an IC50 value of 0.54 μM
體內(nèi)研究(In Vivo)
Bumetanide (7.6-30.4 mg/kg; i.v.) attenuates the decrease in apparent diffusion coefficients (ADC) ratios for both cortex and striatum (by 40-67%), indicating reduced edema formation[3].
Bumetanide also reduces infarct size[3].
Bumetanide shows different half-lives of 21.4 min, 53.8 min and 137 min following 2 mg/kg, 8 mg/kg and 20 mg/kg intravenous injection, respectively, in rats
| Animal Model: | Normotensive Sprague-Dawley rats (250-300 g)[3] |
| Dosage: | 7.6 mg/kg, 15.2 mg/kg, 30.4 mg/kg |
| Administration: | Intravenous injection |
| Result: | Reduced the middle cerebral artery occlusion (MCAO)-induced decrease in ADC values in all four ipsilateral regions (L1-L4). |
| Animal Model: | Male Sprague-Dawley rats (220-300 g)[4] |
| Dosage: | 2 mg/kg, 8 mg/kg, 20 mg/kg (Pharmacokinetic Analysis) |
| Administration: | Intravenous administration |
| Result: | T1/2 (21.4 min, 53.8 min and 137 min for 2 mg/kg, 8 mg/kg and 20 mg/kg, respectively ) |
分子量：364.42
Formula：C17H20N2O5S
CAS 號：28395-03-1
中文名稱：布美她尼；5-正丁氨基-4-苯氧基-3-氨基磺?；郊姿?；3-(氨基磺?；?-5-(丁基氨基)-4-苯氧基苯甲酸；3-正丁胺基-4苯氧基-5-氨基磺酰苯甲酸
運輸條件：Room temperature in continental US; may vary elsewhere.
儲存方式
4°C, protect from light
*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
溶解性數(shù)據(jù)
DMSO : 100 mg/mL (274.41 mM; Need ultrasonic)
H2O : 0.1 mg/mL (0.27 mM; Need ultrasonic)
| 濃度溶劑體積質(zhì)量 | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.7441 mL | 13.7204 mL | 27.4409 mL |
| 5 mM | 0.5488 mL | 2.7441 mL | 5.4882 mL |
| 10 mM | 0.2744 mL | 1.3720 mL | 2.7441 mL |
請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
儲備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (protect from light)。-80°C 儲存時，請在 6 個月內(nèi)使用，-20°C 儲存時，請在 1 個月內(nèi)使用。
以下溶解方案都請先按照 In Vitro 方式配制澄清的儲備液，再依次添加助溶劑：
——為保證實驗結(jié)果的可靠性，澄清的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的工作液，建議您現(xiàn)用現(xiàn)配，當天使用； 以下溶劑前顯示的百
分比是指該溶劑在您配制終溶液中的體積占比；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的方式助溶
- 1.
請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (6.86 mM); Clear solution
- 2.
請依序添加每種溶劑： 10% DMSO 90% corn oil
Solubility: ≥ 2.5 mg/mL (6.86 mM); Clear solution
參考文獻
[1]. Lykke K, et al. The search for NKCC1-selective drugs for the treatment of epilepsy: Structure-function relationship of bumetanide and various bumetanide derivatives in inhibiting the human cation-chloride cotransporter NKCC1A. Epilepsy Behav. 2016 Jun;59:42-9.
[2]. Ciaran Richardson, et al. Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways. J Cell Sci. 2011 Mar 1;124(Pt 5):789-800.
[3]. Martha E O'Donnell, et al. Bumetanide inhibition of the blood-brain barrier Na-K-Cl cotransporter reduces edema formation in the rat middle cerebral artery occlusion model of stroke. J Cereb Blood Flow Metab. 2004 Sep;24(9):1046-56.
[4]. S H Lee, et al. Pharmacokinetics and pharmacodynamics of bumetanide after intravenous and oral administration to rats: absorption from various GI segments. J Pharmacokinet Biopharm. 1994 Feb;22(1):1-17.6
注：產(chǎn)品僅用于科研
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