KRN4884
目录号 : GC32629
KRN4884是一种K+通道开放剂。在细胞内ATP(1mM)存在下，KRN4884(0.1-3μM)激活KATP通道(EC50=0.55μM),这种作用存在浓度依赖性。
Cas No.:152802-84-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | KRN4884 is dissolved in DMSO as a 10 mM stock solution, and diluted in the bath solution. The final concentration of DMSO to which cells are exposed is less than 0.1%[1]. To quantitatively analyze the effect of KRN4884 or other compounds, channel activity is expressed as NPoi. NPoi is calculated by integrating a 5- to 15-s continuous current record during the steady effect of each drug. The concentration-response curve for KRN4884 is obtained by normalizing NPoi to that obtained by superfusing with the ATP-free bath solution, and fit to a Hill equation[1]. |
Animal experiment: | Rats[2] Five-week old male Sprague-Dawley (Crj; CD) rats are obtained and housed in a temperature-controlled environment with a 12 h daily light cycle with free access to water and chow (CE-2). At 6-weeks old, the animals are assigned to vehicle, Clofibrate (160 mg/kg) or KRN4884 (3 mg/kg) treatment groups. The drug is given daily, by gavage for 10 days at 2 mL/kg as a suspension in 0.5% (w/v) carboxymethyl cellulose. Systolic blood pressure is determined 1 h after administration on day 9 with the tail cu. method by use of a sphygmomanometer. Four hours after the final administration of the drug or vehicle on day 10, non-fasting blood is collected from an abdominal aorta of each rat under ether anaesthesia. Serum is provided for lipid analysis. Epididymal adipose tissue, thigh muscle, and liver are removed and weighed, then immediately immersed in liquid nitrogen and stored at -80°C until use. Epididymal adipose tissue and thigh muscle are used for determining lipoprotein lipase (LPL) activity and the liver is used for de- termining hepatic triglyceride lipase (HTGL) activity. |
References: [1]. Shinbo A, et al. Activation of cardiac ATP-sensitive K+ channels by KRN4884, a novel K+ channel opener. J Pharmacol Exp Ther. 1997 Nov;283(2):770-7. | |
KRN4884 is a K+ channel opener. In the presence of intracellular ATP (1 mM), KRN4884 (0.1-3 μM) activates KATP channels in a concentration-dependent manner (EC50=0.55 μM).
KRN4884 (0.3 μM) shifts the concentration-response relationship for ATP-induced KATP channel inhibition to the right and slightly upward direction without altering the slope. After either the spontaneous or Ca2+-induced channel rundown, KRN4884 (1 and 3 μM) partially restores the KATP channel activity. Furthermore, the effect of KRN4884 is augmented by the presence of uridine 5′-diphosphate (3 mM). KRN4884 activates cardiac KATP channels through not only decreasing the sensitivity of the channel to ATP but also directly stimulating the opening of the channel. KRN4884 (0.3 and 3 μM) increases the outward current in a concentration-dependent manner, and the unitary current amplitudes are similar to that of KATP channels in the ATP-free solution[1].
The effects of KRN4884, a novel pyridinecarboxamidine type KATP channel opener, on serum triglyceride levels are investigated in Sprague-Dawley rats. Oral administration of KRN4884 (3 mg/kg) for 10 days causes a significant reduction in serum triglyceride levels, which is comparable to that of Clofibrate (160 mg/kg). Reduction in serum triglyceride levels by KRN4884 and Clofibrate are accompanied by a reduction in triglyceride levels both in chylomicron and in very low density lipoprotein. KRN4884 treatment does not affect serum concentrations of total cholesterol and phospholipid, but increases free fatty acid levels. Rats receiving KRN4884 exhibite an increase in lipoprotein lipase (LPL) activity both in adipose tissue and in skeletal muscle[2].
[1]. Shinbo A, et al. Activation of cardiac ATP-sensitive K+ channels by KRN4884, a novel K+ channel opener. J Pharmacol Exp Ther. 1997 Nov;283(2):770-7. [2]. Yokoyama T, et al. Effects of KRN4884, a novel pyridinecarboxamidine type KATP channel opener, on serum triglyceride levels in rats. Br J Pharmacol. 1997 Apr;120(8):1471-6.
| Cas No. | 152802-84-1 | SDF | |
| Canonical SMILES | N#C/N=C(C1=CC(N)=CN=C1)/NCCC2=CC=CC=C2Cl | ||
| 分子式 | C15H14ClN5 | 分子量 | 299.76 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.336 mL | 16.68 mL | 33.36 mL |
| 5 mM | 0.6672 mL | 3.336 mL | 6.672 mL |
| 10 mM | 0.3336 mL | 1.668 mL | 3.336 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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KRN4884, a novel K channel opener: antihypertensive effects in conscious renal hypertensive dogs
J Cardiovasc Pharmacol 1997 Jun;29(6):814-9.PMID:9234664DOI:10.1097/00005344-199706000-00016.
We examined the antihypertensive effects of KRN4884, 5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarbocamidine+ ++, in normotensive dogs, a high-renin model acute renal hypertensive dog (RHD), and a low-renin model chronic RHD in the conscious state, compared with levcromakalim and nilvadipine. KRN4884 decreased mean blood pressure (MBP) at a dose of 0.1 mg/kg p.o. in normotensive dogs and both RHDs. The decrease in MBP was greater in both RHDs than in normotensive dogs, and there were no significant differences between the two RHDs. A transient increase in heart rate (HR) accompanied the increase in MBP in all three types of dogs. In the chronic RHD, KRN4884 at doses of 0.05, 0.1, and 0.2 mg/kg produced a dose-dependent decrease in MBP. The antihypertensive effect of KRN4884 (0.1 mg/kg) was similar to those of levcromakalim (0.05 mg/kg) and nilvadipine (1.0 mg/kg) in magnitude and more prolonged than those of the compounds. The tachycardia induced by KRN4884 was similar to that induced by levcromakalim and was stronger than that induced by nilvadipine. In the 15-day repeated oral-administration study, KRN4884 (0.1 mg/kg) induced sustained hypotensive effects and transient increases in HR and plasma renin activity. No tolerance to the antihypertensive effect of KRN4884 was observed during a 15-day repeated dosing period. After withdrawal of KRN4884, no rebound phenomena in MBP and HR were observed. Neither the maximal concentration nor area under the curve (AUC) of KRN4884 in plasma were changed at days 1, 8, and 15. These data indicate that KRN4884 produces a strong and persistent antihypertensive response in both low-renin and high-renin models of RHD in a conscious state, which suggests that KRN4884 may be useful as an antihypertensive agent.
Effects of potassium channel opener KRN4884 on human conduit arteries used as coronary bypass grafts
Br J Clin Pharmacol 2000 Aug;50(2):154-60.PMID:10930967DOI:10.1046/j.1365-2125.2000.00235.x.
Aims: The effects of a new potassium channel opener KRN4884 on human arteries have not been studied. This study was designed to investigate the effects of KRN4884 on the human internal mammary artery (IMA) in order to provide information on possible clinical applications of KRN4884 for preventing and relieving vasospasm of arterial grafts in coronary artery bypass grafting. Methods: IMA segments (n = 140) taken from patients undergoing coronary surgery were studied in the organ chamber. Concentration-relaxation curves for KRN4884 were established in the IMA precontracted with noradrenaline (NA), 5-hydroxytryptamine (5-HT), angiotensin II (ANG II), and endothelin-1 (ET-1). The effect of glibenclamide (GBC) on the KRN4884-induced relaxation was also examined in NA or 5-HT-precontracted IMA. Concentration-contraction curves for the four vasoconstrictors were constructed without/with pretreatment of KNR4884 (1 or 30 microM) for 15 min. Results: KRN4884 induced less relaxation (P < 0.05) in the precontraction induced by ET-1 (72.9 +/- 5.5%) than by ANG II (94.2 +/- 3.2%) or NA (93.7 +/- 4.1%) with lower EC50 (P < 0.05) for ANG II (-8.54 +/- 0.54 log M) than that for NA (-6.14 +/- 0.15 log M) or ET-1 (-6.69 +/- 0.34 log M). The relaxation in the IMA pretreated with GBC was less than that in control (P < 0.05). KRN4884-pretreatment significantly reduced the contraction (P < 0.05) induced by NA (151.3 +/- 18.4% vs 82.7 +/- 8. 7%), 5-HT (82.7 +/- 12.2% vs 30.1 +/- 7.3%), and ANG II (24.3 +/- 6. 3% vs 5.4 +/- 1.6%), but did not significantly reduce the contraction induced by ET-1 (P > 0.05). Conclusion: KRN4884 has marked vasorelaxant effects on the human IMA contracted by a variety of vasoconstrictors and the effect is vasoconstrictor-selective.
Protective effect of the K+ channel opener KRN4884 on peripheral occlusive arterial disease in rats
Gen Pharmacol 1998 Jul;31(1):59-62.PMID:9595280DOI:10.1016/s0306-3623(97)00429-1.
1. The effect of the potassium channel opener KRN4884 on the peripheral arterial occlusion model induced by laurate was examined and compared with that of beraprost sodium and nilvadipine. 2. KRN4884 or beraprost sodium prevented macroscopic changes in the paw after the injection of laurate. In contrast, nilvadipine did not improve the lesions. 3. KRN4884 produced a dose-dependent increase in gastrocnemius blood flow in the chronic femoral artery-ligated rats. The effect of KRN4884 on the blood flow was stronger in the hypoxic muscle than in the normal muscle. 4. KRN4884 did not have a direct antiplatelet aggregation activity. 5. These findings suggest that KRN4884 is useful for the therapy of peripheral arterial occlusive disease and that the effect of KRN4884 is associated with an increase in blood flow in ischemic skeletal muscle.
Activation of cardiac ATP-sensitive K+ channels by KRN4884, a novel K+ channel opener
J Pharmacol Exp Ther 1997 Nov;283(2):770-7.PMID:9353397doi
In the present study, we have investigated the mechanism underlying the activation by 5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3- pyridinecarboxamidine (KRN4884), a new K+ channel opener, of ATP-sensitive K+ (KATP) channels in single ventricular cells of guinea pig hearts by the inside-out patch-clamp method. In the presence of intracellular ATP (1 mM), KRN4884 (0.1-3 microM) activated KATP channels in a concentration-dependent manner (EC50 = 0.55 microM) without affecting the unitary current conductance and the gating properties. KRN4884 (0.3 microM) shifted the concentration-response relationship for ATP-induced KATP channel inhibition to the right and slightly upward direction without altering the slope. After either the spontaneous or Ca++-induced channel rundown, KRN4884 (1 and 3 microM) partially restored the KATP channel activity. Furthermore, the effect of KRN4884 was augmented by the presence of uridine 5'-diphosphate (3 mM). The results indicate that KRN4884 activates cardiac KATP channels through not only decreasing the sensitivity of the channel to ATP but also directly stimulating the opening of the channel.
Effects of the K+ channel opener KRN4884 on the cardiovascular metabolic syndrome model in rats
J Cardiovasc Pharmacol 2000 Feb;35(2):287-93.PMID:10672863DOI:10.1097/00005344-200002000-00017.
We examined the effects of the potassium channel opener KRN4884 (5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine ) on cardiovascular metabolic syndrome (i.e., syndrome X), in rats. High-fructose diet rats developed hypertension, hypertriglyceridemia, increased total cholesterol/HDL (high-density lipoprotein)-cholesterol ratio, and hyperinsulinemia, KRN4884 (0.3-3.0 mg/kg, twice a day for 14 days, p.o.) alleviated the risk factors in fructose-fed rats. Furthermore, fructose-fed rats exhibited impairment of glucose tolerance and excess insulin secretion when loaded with glucose orally. Treatment with KRN4884 (1.0 mg/kg, twice a day for 14 days, p.o.) improved the glucose intolerance and inhibited hypersecretion of insulin in the glucose-loaded, fructose-fed rats. In contrast, KRN4884 (0.3-1.0 mg/kg, twice a day for 10 days, p.o.) did not affect serum triglyceride, cholesterol, glucose, or insulin concentrations in normal rats. LPL (lipoprotein lipase) activities in skeletal muscle and adipose tissue, and HTGL (hepatic triglyceride lipase) activity in liver were measured after administration of KRN4884 or vehicle twice a day for 14 days in fructose-fed rats. KRN4884 caused a significant increase in LPL activity in muscle and tended to increase LPL activity in adipose tissue in fructose-fed rats. HTGL was decreased in fructose-fed rats as compared with normal controls and was unaffected by KRN4884. These findings suggested that KRN4884 enhances insulin sensitivity and LPL activity, which are related to glucose and lipid metabolism and may be useful for the treatment of syndrome X.