necroptosis-in-3

Necroptosis-IN-3 (Cyclohexanecarboxamide, N-(2-thienylmethyl)-) (Compound 69) is a Necroptosis inhibitor that inhibits TNF-α induced necroptosis. Necroptosis-IN-3 (Compound STX1638) also inhibits 11β-HSD1.

HDAC8-IN-14 is a curcumin derivative serving as a selective HDAC8 inhibitor with a Ki of 9 nM. It induces reactive oxygen species (ROS) production, disrupts mitochondrial membrane potential, and promotes apoptosis. Furthermore, HDAC8-IN-14 significantly triggers cell accumulation in the sub-G0/G1 phase, indicative of apoptosis or necroptosis. It upregulates cytochrome c, cleaved caspase-3, and pro-apoptotic protein Bak expression, while maintaining anti-apoptotic protein Bcl-2 levels unchanged, making it a valuable compound for leukemia research.

Chlorido[N,N'-disalicylidene-1,2-phenylenediamine]iron(III) is a Schiff base-iron(III) complex with potential photosensitizing activity. It triggers tumor cell apoptosis by efficiently catalyzing intracellular ROS bursts under specific irradiation, leading to severe oxidative damage and mitochondrial dysfunction.

NecroIr1, an iridium(III) complex, acts as a necroptosis inducer in Cisplatin-resistant lung cancer cells (A549R). It selectively targets mitochondria, causing oxidative stress and reducing mitochondrial membrane potential (MMP). By activating receptor-interacting serine-threonine kinase 3 (RIPK3) and Mixed Lineage Kinase (MLKL), and modulating CDK4 expression, NecroIr1 facilitates cell death mechanisms [1].

NecroIr2, an iridium(III) complex, functions as a necroptosis inducer in cisplatin-resistant lung cancer cells (A549R). It preferentially accumulates in mitochondria, causing oxidative stress and a reduction in mitochondrial membrane potential (MMP). Moreover, NecroIr2 initiates the activation of receptor-interacting serine/threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like pseudokinase (MLKL), while also regulating CDK4 expression [1].

RIPK3-IN-3 (compound 20) is a selective RIPK3 inhibitor with a potent IC50 value of 10 nM, effectively blocking RIPK3-mediated phosphorylation of MLKL, preventing oligomerization and necroptosis induction. Moreover, RIPK3-IN-3 suppresses CXCL5 secretion and impedes AsPC-1 cell migration and invasion [1].

Citronellol-d3 ((±)-Citronelloll-d3) is the deuterium-labeled form of Citronellol. Citronellol ((±)-Citronellol) acts as an orally effective apoptosis inducer. It can prevent oxidative stress, mitochondrial dysfunction, and apoptosis in the Parkinson's disease model of SH-SY5Y cells induced by 6-OHDA through the regulation of ROS-NO, MAPK/ERK, and PI3K/Akt signaling pathways. Additionally, Citronellol induces necroptosis in human lung cancer cells via the TNF-α pathway and reactive oxygen species (ROS) accumulation. It modulates the autophagy pathway by reducing LC-3 and p62 levels, inhibiting oxidative stress and neuroinflammation, thus offering neuroprotective effects in rat models of Parkinson's disease. Furthermore, Citronellol exhibits antifungal activity against Trichophyton rubrum by inhibiting ergosterol synthesis.