TPP2a (bromide)

TPP2a bromide is a thioredoxin reductase (TrxR) inhibitor with an IC₅₀ value of 1.16 μM, and also acts as a TrxR-specific fluorescent probe with environment-sensitive fluorescence. TPP2a bromide selectively forms covalent interactions with subcellular mitochondrial TrxR, thereby modifying its Sec498 residue. TPP2a bromide can increase the level of reactive oxygen species (ROS) in cells and induce mitochondrial apoptosis in cancer cells. TPP2a bromide exhibits enhanced cytotoxicity against cancer cell lines. TPP2a bromide can be used in research related to cervical cancer, lung cancer, etc^[1]. In Vitro:TPP2a (5 min at 25 °C) potently inhibits purified mammalian TrxR with an IC₅₀ of 1.16 μM^[1].
TPP2a (24 h) potently inhibits mitochondrial TrxR isolated from HeLa cells with an IC₅₀ of 1.44 μM, a 16.8-fold improvement over its parental compound 2a^[1].
TPP2a selectively and covalently binds to the Sec498 residue of TrxR, as demonstrated by fluorescent labeling of TrxR in HeLa cell lysates and purified TrxR samples, and dose-dependent inhibition of BIAM labeling at pH 6.5^[1].
TPP2a (1.0 μM; 6 h) selectively localizes to the mitochondria of living HeLa cells, as shown by colocalization with MitoTracker Red in confocal microscopy images^[1].
TPP2a, when coupled with a Cu²⁺-based nonspecific signal quenching strategy, acts as a selective fluorescent probe for TrxR, exhibiting specific fluorescence in purified TrxR samples, TrxR-depleted HeLa cell lysates, and living HeLa cells with intact mitochondrial TrxR^[1].
TPP2a (48 h) potently inhibits the growth of HeLa, PC3, A549, Bel-7402, MDA-MB-231, and SW480 human cancer cell lines with IC₅₀ values ranging from 0.91 μM to 2.77 μM, with HeLa cells being the most sensitive^[1].
TPP2a (0.1-2.5 μM; 6 h) dose-dependently increases superoxide anion and hydrogen peroxide levels in HeLa cells after 6 h of incubation, with maximal effects observed at 2.5 μM^[1].
TPP2a (0.1-2.5 μM; 24-48 h) dose-dependently induces apoptosis in HeLa cells via the intrinsic mitochondrial pathway, with 96.80% total apoptotic cells observed at 2.5 μM, accompanied by decreased mitochondrial membrane potential, altered Bcl-2 family protein expression, and activation of caspase and PARP cleavage^[1].