EIPA (L593754) is a TRPP3 channel inhibitor (IC50=10.5 μM) and an inhibitor of Na+/H+ exchange (NHE). EIPA inhibits megacytosis, promotes autophagy, and can be used in inflammation and tumor studies.

TRPP3 channel:10.5 μM

METHODS: Ten cells were pretreated with EIPA (50 µM) for 1.5 h. Dextran index was measured by Dextran uptake assay.
RESULTS: Immortalized but untransformed hTERT-HME1 mammary epithelial cells and MCF10A cells did not exhibit megacellular drinking in complete medium, but stimulated dextran uptake by nutrient deprivation. Although PIK3CB was found to be required for growth factor-stimulated macrocytosis, oncogenic mutations in PIK3CA were sufficient to induce constitutive macrocytosis in mouse embryonic fibroblast MEFs and untransformed MCF10A cells. [1]
METHODS: MKN28 cells were treated with EIPA (5-100 µM) for 48 h. Cell proliferation was detected by cell count.
RESULTS: Cell exposure to EIPA inhibited the proliferation of MKN28 cells in a dose- and time-dependent manner. [2]

METHODS: To assay in vivo activity, EIPA (10 mg/kg) was injected intraperitoneally into BALB/c mice bearing 4T1 xenografts, and 70 kD FITC-Ficoll was injected into the tumors 1 h later. The mice were necropsied 1 h after Ficoll injection, and the tumors were excised and frozen in OCT.
RESULTS: EIPA-sensitive 70 kD FITC-Ficoll uptake was observed in in situ homozygous 4T1 tumors of BALB/c mice, suggesting that AMPK activation or other signals are sufficient to trigger the formation of large fusions in vivo. [1]

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].