EIPA (L593754) (L593754, MH 12-43) is a TRPP3 channel inhibitor (IC50: 10.5 μM). It also inhibits Na+/H+-exchanger (NHE) and macropinocytosis.

It is found that EIPA, benzamil, and phenamil rapidly and reversibly block Ca2+-activated TRPP3 channel activation at -50 mV, with IC50s of 143, 10.5, 1.1, and 0.14 μM, respectively[1]. The number of autophagic vacuoles increases dramatically in the HAE and HPE groups after EIPA treatment compares with the HAN and HPN groups. EIPA regulates the initiation and maturation of the autophagy associated with amino acids in IEC-18 cells [2]. In addition, the uptake of cinnamoylphenazine (CA-PZ) and neutral red (NR) is inhibited by EIPA [3].

The effect of EIPA alone (without alanine or proline) is also examined in both control (DMEM cultured cells) and amino acid-starved cells. The cells are incubated for 6 h in DMEM containing 5% FBS and either 0 or 0.3 mM EIPA (labeled QNN and QNE, respectively), HBSS containing either 0 or 0.3 mM EIPA (labeled HNN and HNE, respectively), HBSS with 1.0 mM alanine (labeled HAN) or 0.5 mM proline (labeled HPN), HBSS with 1.0 mM alanine and 0.3 mM EIPA (labeled HAE), and HBSS with 0.5 mM proline and 0.3 mM EIPA (labeled HPE) [2].