EIPA (Synonyms: L-593,754, MH 12-43, 5-(N-ethyl-N-isopropyl)-Amiloride)

EIPA inhibited TRPP3-mediated Ca2+-activated currents with IC50 values of 10.5 µM ^[1]. TRPP3, a member of the transient receptor potential (TRP) superfamily of cation channels, is a Ca2+-activated channel permeable to Ca2+, Na+, and K+ ^[1].EIPA (5-(N-ethyl-N-isopropyl)-amiloride) is a commonly used amiloride derivative modified similarly to MPA, and its Ki for NHE1, NHE2, and NHE3 are 0.3, 1.8, and 67 µM, respectively^[2,3]

EIPA suppressed proliferation of MKN28 cells through up-regulation of p21 expression via reduction of [Cl- ] c as a result from DIDS-sensitive Cl- /HCO3- exchanger-mediated compensation for keeping pHc normal under an NHE-inhibited condition ^[4].

EIPA preischemic treatment overcame the I/R-induced renal dysfunction. Histologic examination of the kidney of vehicle-treated ARF mice revealed severe lesions, and these lesions were significantly suppressed by the preischemic treatment with EIPA. In addition, EIPA suppressed the increment of renal ET-1 content after reperfusion ^[5]. EIPA at doses of 3 and 9 mg/kg per day inhibited tumor growth of HepG2 modle mice significantly compared with the control ^[6].

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