EIPA (Synonyms: L-593,754, MH 12-43, 5-(N-ethyl-N-isopropyl)-Amiloride) |
Catalog No.GC15893
One-Click Copy Product Info
|
EIPA는 TRPP3을 통해 중계되는 Ca2 +-activated 전류를 억제했으며, 그 IC50 값은 10.5 µM이다.
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.
EIPA는 TRPP3을 통해 중계되는 Ca2 +-activated 전류를 억제했으며, 그 IC50 값은 10.5 µM이다.TRPP3은 순간적 수용체 전위(TRP) 가정이온 채널 초가족의 구성원으로, Ca2+-활성화 채널이며, Ca2+, Na+, K+에 통과가능한다. EIPA (5-(N-ethyl-N-isopropyl)-amiloride)는 일반적으로 사용되는 아밀로리드 유도체로, MPA와 유사하게 수정되어 있으며, NHE1, NHE2, NHE3에 대한 억제 상수 Ki는 각각 0.3, 1.8, 67µM이다.
EIPA는 NHE-inhibited 조건에서DIDS에 의한 민감성 Cl-/HCO3- 교환체를 통해 pHc를 정상적으로 유지하기 위한 보상으로 인한 [Cl-]c 감소를 통해 p21 발현의 up-regulation을 증가시켜 MKN28 세포의 증식을 억제했다.
EIPA의 뇌졸전 예방 치료는 혈액 공급I/R으로 인한 신장기능장애을 극복했다. 치료제로 치료된 ARF 쥐 신장의 조직학 검사에서 심각한 병변을 발견했으며, 이 병변은 EIPA의 뇌졸전 예방 치료에 의해 현저하게 억제되었다. 또한, EIPA는 재공급 후 신장 ET-1 함량 증가를 억제했다. EIPA는 매일 3mg/㎏ 및 9mg/㎏의 용량으로 HepG2 모델 쥐의 종양 성장을 대조구와 비교하여 상당히 억제했다.
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
| 세포 실험 [1]: | |
세포 라인 | MCF-7 세포 |
제조 방법 | 세포는 6웰 플레이트에 24시간 재배되었으며, 이어서 EIPA(10μM), Akti(1μM), U0126(10μM) 또는 이들의 조합으로 48시간 동안 처리되었습니다. |
반응 조건 | 10µM ,48 시간 동안 |
응용 분야 | MCF-7 세포는 EIPA 처리를 받았으며, ERK 및 Akt 억제제를 사용한 경우와 사용하지 않은 경우 모두 실험되었습니다. EIPA 처리 시 ERK 활성이 증가했지만, Akt 활성은 그렇지 않았으며, 두 킨아이즈는 각각의 억제제 U0126과 Akti에 의해 효과적으로 억제되었습니다. 특히, ERK 억제는 EIPA 유도된 CHOP 상향 조절 및 PARP 절단을 크게 강화했습니다. |
| 동물 실험 [2]: | |
동물 모형 | 7주령의 암컷 동형 결합 BALB/c Nu/Nu 무모피 쥐는 양 측엉에 피하 주사(s.c.)하여 10^6개의 본가 및 IKKαδ MIA PaCa-2 세포 또는 1334와 1444 세포를 1:1 농도로 BD Matrigel(BD Biosciences)과 혼합하여 총량 100 μl로 주사하였습니다. |
제조 방법 | 종양의 부피가 평균 50-100 mm3에 도달했을 때 쥐는 차량(PBS에 DMSO), EIPA(7.5 mg/kg), MRT68921(10 mg/kg) 또는 MRT68921+EIPA로 15일 동안 처리되었습니다. |
제형 | s.c., 7.5 mg/kg/d, 7 일 동안 |
응용 분야 | 1개월 크기에서 시작된 1개월간의 EIPA 치료는 팬크레아의 무게를 현저하게 감소시켰으며(종양 부담을 대체하는 지표), 샘조직에서 댐으로의 변생(ADM)과 고급 PanIN 형성을 억제하고 KrasG12D;IkkαδPEC 쥐에서 정상적인 팬크레아실질을 유지했으며, 동시에 MP를 감소시켰습니다. |
참고문헌: [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[2]: H. Su, F. Yang, R. Fu, et al. Cancer cells escape autophagy inhibition via NRF2-induced micropinocytosis. Cancer Cell, 39 (5) (2021), pp. 678-693, 10.1016/j.ccell.2021.02.016 | |
| Cas No. | 1154-25-2 | SDF | |
| Synonyms | 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 |
| Solubility | 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.)