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.

Chlorido[N,N'-disalicylidene-1,2-phenylenediamine]iron(III) is an inducer of ferroptosis.1 It induces ferroptosis, but not apoptosis or necroptosis, in NB1 cancer cells when used at a concentration of 3 μM.1 Chlorido[N,N'-disalicylidene-1,2-phenylenediamine]iron(III) inhibits proliferation of BJAB, NALM-6, Jurkat, MelHO, and MCF-7 cancer cells (IC50s = 0.07, 2.5, 1.5, 3, and 5 μM, respectively), as well as NALM-6 cells resistant to daunorubicin and vincristine when used at concentrations ranging from 0.04 to 0.125 μM.2 |1. Sagasser, J., Ma, B., Baecker, D., et al. A new approach in cancer treatment: Discovery of chlorido[N,N'-disalicylidene-1,2-phenylenediamine]iron(III) complexes as ferroptosis inducers. J. Med. Chem. 62(17), 8053-8061 (2019).|2. Lee, S.-Y., Hille, A., Kitanovic, I., et al. [FeIII(salophene)Cl], a potent iron salophene complex overcomes multiple drug resistance in lymphoma and leukemia cells. Leuk. Res. 35(3), 387-393 (2011).

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].