EIPA (Synonyms: L-593,754, MH 12-43, 5-(N-ethyl-N-isopropyl)-Amiloride) |
カタログ番号GC15893
One-Click Copy Product Info
|
EIPAはTRPP3を介したCa2+活性化電流を10.5 µMのIC50値で阻害した。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1154-25-2
Sample solution is provided at 25 µL, 10mM.
EIPAはTRPP3を介したCa2+活性化電流を10.5 µMのIC50値で阻害した。カチオンチャネルの一過性受容体電位（TRP）スーパーファミリーのメンバーであるTRPP3は、Ca2+、Na+、K+に透過性のCa2+活性化チャネルである。EIPA (5-(N-ethyl-N-isopropyl)-amiloride)は、MPAと同様に修飾された一般的に使用されるアミロリド誘導体であり、NHE1、NHE2、NHE3に対するKiはそれぞれ0.3、1.8、67μMである。
EIPAは、NHE阻害条件下でpHcを正常に保つためのDIDS感受性Cl- /HCO3-交換体を介した補償の結果として、[Cl- ] cの減少を介してp21発現のアップレギュレーションを介してMKN28細胞の増殖を抑制した。
EIPAによる虚血前処置は、I/R誘発腎機能障害を克服した。ビヒクル投与したARFマウスの腎臓の組織学的検査では、重篤な病変が認められ、これらの病変はEIPAによる虚血前処置によって有意に抑制された。さらに、EIPAは再灌流後の腎ET-1含量の増加を抑制した[5]。EIPAを3mg/kgおよび9mg/kg/日投与すると、HepG2モデルマウスの腫瘍増殖がコントロールと比較して有意に抑制された。
References:
[1]. Dai XQ, Ramji A, Liu Y, Li Q, Karpinski E, Chen XZ (2007) Inhibition of TRPP3 channel by amiloride and analogs. Mol Pharmacol 72:1576-1585
[2]. Guffey, S.C.; Fliegel, L.; Goss, G.G. Cloning and characterization Na+/H+ Exchanger isoforms, NHE2 and, NHE3 from the gill Pacific dogfish, Squalus suckleyi. Comp. Biochem. Physiol. Part B Biochem. Mol. Biol. 2015, 188, 46-53.
[3]. Masereel, B. An overview inhibitors Na+/H+ exchanger. Eur. J. Med. Chem. 2003, 38, 547-554.
[4]. Hosogi SMH, Nakajima K, Ashihara E, Niisato N, Kusuzaki K, Marunaka Y: An inhibitor of Na(+)/H(+) exchanger (NHE), ethyl-isopropyl amiloride (EIPA), diminishes proliferation of MKN28 human gastric cancer cells by decreasing the cytosolic Cl(-) concentration via DIDS-sensitive pathways. Cell Physiol Biochem. 2012, 30: 1241-1253. 10.1159/000343315.
[5]. Yamashita J, Ohkita M, Takaoka M, Kaneshiro Y, Matsuo T,Kaneko K, Matsumura Y.Role of Na+/H+ exchanger in the pathogen-esis of ischemic acute renal failure in mice.J Cardiovasc Pharmacol49:154 -160, 2007.
[6]. X. Yang, D. Wang, W. Dong, Z. Song, K. Dou.Expression and modulation of Na+/H+ exchanger 1 gene in hepatocellular carcinoma: a potential therapeutic target. J. Gastroenterol. Hepatol., 26 (2) (2011), pp. 364-370
| 細胞実験[1]: | |
細胞株 | MCF-7細胞 |
準備方法 | 細胞は、EIPA（10 µM）、Akti（1 µM）、U0126（10 µM）またはその組み合わせで48時間処理する前に、6ウェルプレートに24時間播種された。 |
反応条件 | 10 µMで48時間 |
アプリケーション | MCF-7細胞は、ERKおよびAkt阻害剤の有無でEIPA処理された。EIPA処理によりERK活性は増加したが、Akt活性は増加しなかった。両キナーゼはそれぞれの阻害剤（U0126およびAkti）で効果的に阻害された。驚くべきことに、ERK阻害はEIPAによるCHOPのアップレギュレーションおよびPARP切断を強力に増強した。 |
| 動物実験 [2]: | |
動物モデル | 雌のホモ接合性BALB/c Nu/Nuヌードマウスは、7週齢で、106個の親株およびIKKαδ MIA PaCa-2細胞または1334および1444細胞をBD Matrigel（BD Biosciences）と1:1の割合で混合し、総容量100 µLで両側腹部皮下に注射された。 |
準備方法 | 腫瘍が平均50-100 mm3の体積に達したとき、マウスは15日間、ビヒクル（PBS中のDMSO）、EIPA（7.5 mg/kg）、MRT68921（10 mg/kg）、またはMRT68921+EIPAで処理された。 |
投与形態 | 皮下、7.5 mg/kg/日で7日間 |
アプリケーション | 1か月齢で開始された1か月間のEIPA治療は、膵臓重量（腫瘍負荷の代替指標）を著しく減少させ、腺房から管状への転生（ADM）および進行したPanIN形成を抑制し、正常な膵臓実質を保持し、KrasG12D;IkkαδPECマウスにおけるMPを減少させた。 |
参考文献: [1]: M.G. Rolver, L.O. Elingaard-Larsen, A.P. Andersen, L. Counillon, S.F. Pedersen. Pyrazine ring-based Na+/H+ exchanger (NHE) inhibitors potently inhibit cancer cell growth in 3D culture, independent of NHE1.Sci. Rep., 10 (2020), p. 5800 | |
| Cas No. | 1154-25-2 | SDF | |
| 同義語 | L-593,754, MH 12-43, 5-(N-ethyl-N-isopropyl)-Amiloride | ||
| Chemical Name | 3-amino-6-chloro-N-(diaminomethylene)-5-(ethyl(isopropyl)amino)pyrazine-2-carboxamide | ||
| Canonical SMILES | ClC1=NC(C(/N=C(N)\N)=O)=C(N)N=C1N(CC)C(C)C | ||
| Formula | C11H18ClN7O | M.Wt | 299.76 |
| 溶解度 | 14mg/mL in DMSO, 20mg/mL in DMF, 2mg/mL in Ethanol | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.336 mL | 16.68 mL | 33.36 mL |
| 5 mM | 667.2 μL | 3.336 mL | 6.672 mL |
| 10 mM | 333.6 μL | 1.668 mL | 3.336 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
-
Related Biological Data
Studying the cell entry pathway of Antimir21-RNP-Apt. (a) The probability of observing a force–time signal for Antimir21-RNP-Apt entry into HEK-293 cells and MDA-MB-231 cells (before and after inhibition).
After adding the inhibitors namely EIPA(GLPBIO)(10 μM), nystatin (10 μg mL−1), filipin III (1 μg mL−1), and CPZ (1 μg mL−1) and incubating for 30 min, the cells were washed with PBS and fresh medium was added to carry out the force tracing experiment.
Nanoscale 14.25 (2022): 8919-8928 PMID: 35699091 IF: 6.7 -
Related Biological Data
STAT3 is constitutively phosphorylated in NHE1 overexpressed gastric cancer cells.NHE1 overexpression induced the increase in the expression of pSTAT3, EIPA reverses the increase. Also, NHE1-siRNA transfection decrease the expression of pSTAT3 (Figure 5A, P<0.01).
NHE1 inhibitor EIPA (25 μM, GLPBIO,) was dissolved and stocked in DMSO and applied to the cells in the culture medium.
Oncotargets Ther 13 (2020): 8521-8532 PMID: 32904684 IF: 4.142
Average Rating: 5 (Based on Reviews and 13 reference(s) in Google Scholar.)