Data for: The neuroprotectant ITH12575 is a selective blocker of neuronal mitochondrial Na+/Ca2+ exchanger (NCLX)

Published: 27 April 2026| Version 1 | DOI: 10.17632/b3t3zm9x4h.1
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These data illustrates the pharmacological characterization of a new mitochondrial Na+/Ca2+ exchanger (NCLX blocker), namely ITH12575. The study of mitochondria and their influence on the cytosolic Ca2+ buffering have become highly relevant in a plethora of physiological and pathological processes, such as neurodegeneration. In this context, the mitochondrial Na+/Ca2+ exchanger was identified as NCLX since 2008. However, the study and characterization of NCLX, has been very complicated due to the absence of drugs able to block it selectively. The widely-used drug CGP37157 presents several issues, such as poor NCLX selectivity and solubility. Thus, the role of NCLX in neuronal death/survival processes remains controversial. During the last decade, we have described new NCLX capable of improving CGP37157 blocking properties. The benzothiazepine ITH12575 has been positioned as the best compound by its potency and selectivity. In the current dataset, we analize ITH12575 in a KO-NCLX animal model, which is also deeply characterized. the interpretation of data show that ITH12575 losses its neuroprotective and calcium-regulating capacities in both KO-NCLX and silenced NCLX in vitro models, what reinforce the idea that the neuroprotection exerted by ITH12575 is exclusively due to NCLX blockade. In addition, we disclose how ITH12575 protects mitochondrial bioenergetic against a calcium-overload insult. Therefore, data herein deposited show: 1) a physiological, morphological and pharmacological characterization of the KO-NLCX animal model used 2) ITH12575 reduced neuronal Ca2+ increases induced by 70 mM KCl in SH-SY57 and NMDA in embryonic rat cortical neurons 3) ITH12575 blocked NMDA-evoked Ca2+ elevations in wild-type mice cortical neurons but not in KO-NCLX mice cortical neurons 4) ITH12575 protected SH-SY5Y cells against rotenone plus oligomycin A cocktail when NCLX was not silenced. 5) Pharmacological blockade of NCLX by ITH12575 prevented mitochondrial bionergetic dysfunction exacertabed by Ca2+ overload

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