EIPA hydrochloride
(Synonyms: L593754 hydrochloride; MH 12-43 hydrochloride) 目录号 : GC35970
EIPA hydrochloride (L593754 hydrochloride) 是一种 TRPP3 channel 抑制剂，其 IC50 值为 10.5 μM。EIPA 还抑制 Na+/H+ 交换器 (NHE) 和巨噬细胞。
Cas No.:1345839-28-2
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >99.00%
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- SDS (Safety Data Sheet)
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EIPA hydrochloride (L593754 hydrochloride) is a TRPP3 channel inhibitor with an IC50 of 10.5 μM[1]. EIPA also inhibits Na+/H+-exchanger (NHE)[2] and macropinocytosis[3]. IC50: 10.5 μM (TRPP3 channel)[1]NHE[2]Macropinocytosis[3]
[1]. Dai XQ, et al. Inhibition of TRPP3 channel by MK-870 and analogs. Mol Pharmacol. 2007 Dec;72(6):1576-85. [2]. Shi H, et al. Na+/H+ Exchanger Regulates Amino Acid-Mediated Autophagy in Intestinal Epithelial Cells. Cell Physiol Biochem. 2017;42(6):2418-2429. [3]. Zhu BY, et al. A new HDAC inhibitor cinnamoylphenazine shows antitumor activity in association with intensive macropinocytosis.
| Cas No. | 1345839-28-2 | SDF | |
| 别名 | L593754 hydrochloride; MH 12-43 hydrochloride | ||
| Canonical SMILES | O=C(C1=NC(Cl)=C(N(CC)C(C)C)N=C1N)NC(N)=N.Cl | ||
| 分子式 | C11H19Cl2N7O | 分子量 | 336.22 |
| 溶解度 | DMSO : 50 mg/mL (166.80 mM; Need ultrasonic) | 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 | 2.9742 mL | 14.8712 mL | 29.7424 mL |
| 5 mM | 0.5948 mL | 2.9742 mL | 5.9485 mL |
| 10 mM | 0.2974 mL | 1.4871 mL | 2.9742 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Superoxide dismutase C affects Dictyostelium contractile vacuole biogenesis and function
Dev Growth Differ 2020 Dec;62(9):516-526.PMID:33118157DOI:10.1111/dgd.12698.
Dictyostelium cells cope with hypo-osmotic stress with a contractile vacuole (CV) system, which consists of one or two vacuoles that cyclically charge and discharge. Uniquely, a F-Actin remodeling dependent minimal mixing of the CV membrane components with the target plasmalemma during the fusion and the dischargement warrants the integrity of the CV bladder for an efficient next CV cycle. The effect of hypo-osmotic stress on F-Actin remodeling activity, however, is currently not well understood. Dictyostelium cells increase the level of intracellular superoxide level in response to hypo-osmotic stress, which in turn activates redox-sensitive Ras proteins, but not Akt, which is one of the Ras downstream targets and a major regulator of F-Actin remodeling. However, Akt is not insulated from the active Ras in cells lacking Superoxide dismutase C (SodC). We report here that sodC- cells were compromised in the CV structure and function and the attenuation of Ras/PI3K/Akt signaling in several independent means significantly improved the compromised CV structure but not the function. Interestingly, when sodC- cells were treated with 5-(N,N-Dimethyl) amiloride hydrochloride (EIPA), an inhibitor of sodium proton exchanger (NHE), both the structure and the function of the CV improved. Thus, a proper CV biogenesis in sodC- cells was insufficient to restore their CV function, which in turn indicates the presence of an additional target for SodC and EIPA that modulates CV function.
Blockade of epithelial sodium channels improves sperm motility in asthenospermia patients
Int J Androl 2009 Aug;32(4):330-6.PMID:18298571DOI:10.1111/j.1365-2605.2008.00864.x.
Epithelial Na(+) channels (ENaCs) are ion channels that play important roles in physiology as well as pathophysiology. Inhibiting ENaCs using amiloride and its derivatives has been suggested in treatment of cardiovascular disease and hypertension. By immunoblotting, we demonstrated the presence of ENaC-alpha protein in the flagellar midpiece of both rat and human sperm. Immunohistochemistry analyses in rat testis localized ENaC-alpha expressed in the Leydig cell, Sertoli cell, Ap spermatogonium, spermatocyte, spermatid and residual body. Importantly, using computer-assisted sperm motility analysis, we first observed that EIPA [5-(N-ethyl-N-isopropyl)-amiloride hydrochloride] inhibition of ENaCs, possibly including ENaC-alpha and ENaC-delta, significantly improved the sperm motility in healthy donors by 14.23% (mean +/- SEM, 68.75 +/- 9.76% vs. 78.53 +/- 6.20%, p < 0.001) and in asthenospermia patients by 115.89% from 9.50 +/- 6.11% to 20.51 +/- 12.13% (mean +/- SEM, p < 0.001). The improved sperm motility by EIPA has important clinical implications in the treatment of asthenospermia and certainly warrants further investigation.
Blockade of peripheral and spinal Na+/H+ exchanger increases formalin-induced long-lasting mechanical allodynia and hyperalgesia in rats
Brain Res 2012 Sep 26;1475:19-30.PMID:22898152DOI:10.1016/j.brainres.2012.08.001.
The Na(+)/H(+) exchanger (NHE) is involved in the regulation of intracellular pH and volume by mediating the electroneutral transport of H(+) against an influx of Na(+) ions. Since NHE1 regulates pH in neurons and astrocytes and it is expressed in nociceptive nerve fibers, it is likely that NHE may modulate neuronal excitability and pain transmission. The purpose of this study was to assess the participation of peripheral and spinal NHE in the secondary allodynia/hyperalgesia induced by formalin. In addition, we determined whether formalin injection modifies the expression of NHE1 in lumbar dorsal root ganglia (DRG) and dorsal spinal cord. Subcutaneous injection of 0.5% formalin into the dorsal surface of the hind paw produced acute nociceptive behaviors (flinching and licking/lifting) followed by long-lasting bilateral secondary mechanical allodynia/hyperalgesia. Peripheral and intrathecal pre-treatment (-10min) with selective NHE inhibitors 5-(N,N-dimethyl)amiloride hydrochloride (DMA, 0.3-30μM), 5-(N-ethyl-N-isopropyl)amiloride (EIPA, 0.3-30μM) and [1-(quinolin-5-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl] guanidine dihydrochloride (zoniporide, 0.03-3μM) significantly increased 0.5% formalin-induced bilateral long-lasting secondary allodynia/hyperalgesia. Contrariwise, local peripheral or intrathecal post-treatment (day 6 postinjection) with these NHE inhibitors did not affect formalin-induced nociceptive behaviors. Formalin injection reduced NHE1 expression in ipsilateral and contralateral spinal dorsal horns from day 1 to 12. In addition, formalin diminished NHE1 protein expression in DRG at day 12. These results suggest that NHE1 plays a role in pain processing at peripheral and spinal levels in formalin-induced long-lasting nociceptive behaviors. Additionally, these results suggest that proteins involved in pH regulation could be targets for the development of new analgesic drugs.
Identification of the Na+/H+ exchanger 1 in dorsal root ganglion and spinal cord: its possible role in inflammatory nociception
Neuroscience 2009 Apr 21;160(1):156-64.PMID:19248819DOI:10.1016/j.neuroscience.2009.02.033.
mRNA and protein presence of Na+/H+ exchanger (NHE) 1 (NHE1) and 5 (NHE5) in dorsal root ganglion (DRG) and dorsal spinal cord as well as its possible role in three inflammatory nociception tests were determined. Local peripheral ipsilateral, but not contralateral, administration of NHE inhibitors 5-(N,N-dimethyl)amiloride hydrochloride (DMA, 0.3-30 microM/paw), 5-(N-ethyl-N-isopropyl)amiloride (EIPA, 0.3-30 microM/paw) and amiloride (0.1-10 microM/paw) significantly increased flinching but not licking behavior in the capsaicin and 5-HT tests. Moreover, DMA and EIPA (0.03-30 microM/paw) as well as amiloride (0.1-1 microM/paw) augmented, in a dose-dependent manner, 0.5% formalin-induced flinching behavior during phase II but not during phase I. Reverse transcription-polymerase chain reaction showed the expression of NHE1 and NHE5 in DRG and dorsal spinal cord. Western blot analysis confirmed the presence of NHE1 in DRG and spinal cord. Moreover, NHE5 was expressed in dorsal spinal cord, but not in DRG where a 45 kDa truncated isoform of NHE5 was identified. Collectively, these data suggest that NHE1, but not NHE5, plays an important role reducing inflammatory pain in rats.
Inhibition of lipopolysaccharide-induced prostaglandin E2 production and inflammation by the Na+/H+ exchanger inhibitors
J Pharmacol Exp Ther 2007 Apr;321(1):345-52.PMID:17237260DOI:10.1124/jpet.106.116251.
We analyzed the effects of the Na+/H+ exchanger (NHE) inhibitor 3,5-diamino-6-chloro-N-(diaminomethylidene)pyrazine-2-carboxamide hydrochloride (amiloride) and its analogs 5-(N,N-dimethyl)-amiloride (DMA) and 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) on the lipopolysaccharide (LPS)-induced production of prostaglandin (PG) E2 in vitro and in vivo. In the mouse macrophage-like cell line RAW 264, these inhibitors suppressed the LPS (1 microg/ml)-induced production of PGE2 at 8 h in a concentration-dependent manner. They also reduced the LPS-induced release of arachidonic acid from membrane phospholipids at 4 h and the LPS-induced increase in the level of cyclooxygenase (COX)-2 protein at 6 h, but not the level of COX-2 mRNA at 3 h. The LPS-induced phosphorylation of mitogen-activated protein kinases and degradation of inhibitor of kappaB-alpha were not inhibited by these drugs. In an air pouch-type LPS-induced inflammation model in mice 30 mg/kg amiloride and 10 mg/kg EIPA as well as the COX inhibitor indomethacin (10 mg/kg), significantly reduced the level of PGE2 in the pouch fluid at 8 h and the vascular permeability from 4 to 8 h. The accumulation of pouch fluid and leukocytes in the pouch fluid at 8 h was significantly inhibited by amiloride and EIPA but not by indomethacin. These findings suggested that the NHE inhibitors suppress the production of PGE2 through inhibiting the release of arachidonic acid and the increase in COX-2 protein levels and thus induce anti-inflammatory activity.