Table 1 Effect of pyrazineguanidine and benzoylguanidine compounds on viability of MCF-7 and MDA-MB-231 spheroids.

	Structure^a	Lipophilicity^b	Reported Ki values for NHE1 (µM)^c	Reported IC₅₀ values for NHE1 (µM)^d	Experimentally determined EC₅₀ values for compound-induced loss of viability (µM)^e
	Structure^a	Lipophilicity^b	Reported Ki values for NHE1 (µM)^c	Reported IC₅₀ values for NHE1 (µM)^d	MCF-7	95% CI	MDA-MB-231	95% CI
Amiloride		0.68 (LogD) 0.93 (LogP)	1.0–7.0	3.7–60	30.5	18.23–42.28	55.8	32.51–81.68
DMA		1.64 (LogD)	0.023–0.5	0.19	16.6	8.47–32.41	59	30.43–114.20
EIPA		3.2 (LogD)	0.01–0.1	0.016–0.8	4.8	1.29–17.78	19.6*	-
HMA		2.94 (LogD)	0.013	—	2.5	0.86–7.33	13.5	4.73–38.34
Cariporide		−1.01 (LogP)	0.008–0.04	0.03–3.4	ND**	ND	ND**	ND
Eniporide		−1.03 (LogP)	—	0.0045–0.38	ND***	ND	ND***	ND

The table displays reported IC₅₀ and Ki values for NHE1 for the tested inhibitors, alongside experimentally obtained EC₅₀ values for compound-induced loss of viability. ^aChemical structure of inhibitors. Blue: pyrazine ring characteristic for pyrazineguanidine compounds. Green: phenyl ring characteristic for benzoylguanidine compounds. Red highlights the different substitutions on the 5-position. ^bThe reported lipophilicity of each compound indicated by LogD and/or LogP values. ^cReported NHE1 Ki values presented in µM. ^dReported NHE1 IC₅₀ values, determined in the presence of 100–130 mM Na⁺, presented in µM. ^eExperimentally obtained EC₅₀ values based on 3 n for each inhibitor. EC₅₀ values were calculated in GraphPad Prism by nonlinear regression using the equation Y = Bottom + (Top-Bottom)/(1 + 10^((X-logIC₅₀))), where X is the logarithm of the inhibitor concentration, top and bottom are the highest and lowest cell viability responses measured, respectively, and Y is the relative cell viability. The corresponding 95% confidence intervals for each EC₅₀ value is presented alongside. ND: not determined. *EC₅₀ calculated from trendline equation generated in Excel. **No effects of concentrations up to 10 µM. ***No effect of concentrations up to 20 µM. Table refs. ^{13,15,17,42,48,49,50,51,56,57,58,59,60,61}.

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