CCDC90A Inhibitors

Chemical inhibitors of CCDC90A function largely by interfering with its role in the mitochondrial calcium uniporter (MCU) complex. Ru360, for instance, is a known specific inhibitor of the MCU complex, directly binding to the MCU and blocking the calcium uptake into mitochondria. By obstructing this pathway, Ru360 functionally inhibits CCDC90A's ability to regulate mitochondrial calcium ion transport. Ruthenium Red operates similarly by preventing mitochondrial calcium uptake, which is an essential function of the CCDC90A within the MCU complex. Furthermore, compounds like KB-R7943 and CGP-37157, though primarily targeting the Na+/Ca2+ exchangers, can indirectly limit the functionality of CCDC90A. KB-R7943 alters intracellular calcium concentration, which is integral to CCDC90A's operation within the MCU, while CGP-37157 by inhibiting the mitochondrial Na+/Ca2+ exchanger can increase mitochondrial calcium, potentially overloading the system and thereby reducing CCDC90A's ability to regulate additional calcium influx.

Other inhibitors such as Gadolinium Chloride and Lanthanum(III) chloride act as general calcium channel blockers, which can indirectly impact CCDC90A by constraining the very calcium fluxes that CCDC90A is designed to mediate in mitochondrial spaces. Similarly, calcium channel blockers like Verapamil, Diltiazem, Nifedipine, and Amlodipine, traditionally used to inhibit L-type calcium channels at the plasma membrane, can also impact intracellular calcium levels, which in turn can affect the mitochondrial calcium homeostasis that CCDC90A helps to maintain. Additionally, 2-APB, an inhibitor of IP3 receptors, modulates the store-operated calcium entry, thereby indirectly influencing CCDC90A by altering intracellular calcium signaling. Lastly, SKF-96365, which inhibits receptor-mediated calcium entry and store-operated calcium channels, can also impact CCDC90A by changing the calcium dynamics within the mitochondria where CCDC90A operates. Each of these chemicals can functionally inhibit CCDC90A by targeting different aspects of calcium regulation and transport, thereby influencing the protein's activity within the mitochondrial environment.