RIP kinase Activator

RIP1/RIP3/MLKL activator 1 (Compound 6i) is a potent anti-glioma agent. RIP1/RIP3/MLKL activator 1 induces necroptosis through RIP1/RIP3/MLKL pathway. RIP1/RIP3/MLKL activator 1 exerts acceptable BBB permeability.

ZBP1/RIP3/MLKL activator 1 (compound 3a) is a synthetically derived quinoline compound. ZBP1/RIP3/MLKL Activator 1 induces DNA damage, enhances intracellular levels of reactive oxygen species (ROS), and triggers apoptosis via the caspase pathway. Furthermore, when apoptosis is inhibited, ZBP1/RIP3/MLKL Activator 1 promotes necroptotic cell death through the ZBP1-RIP3-MLKL pathway. ZBP1/RIP3/MLKL Activator 1 is utilized in oncological research, particularly in the selective targeting of cells with impaired apoptotic function.

RETRA is a RIPK1/RIPK3/MLKL and p73 activator. RETRA mediates plasma membrane disruption, induces ROS accumulation, triggers early mitochondrial hyperpolarization, and synergistically drives necroptosis. RETRA inhibits cancer cells carrying mutant p53 via a p73-dependent salvage pathway. RETRA can be used in research related to cervical cancer and cancers with mutant p53.

NecroIr2 is an iridium(III) complex, serves as necroptosis inducers in Cisplatin (HY-17394)-resistant lung cancer cells (A549R). NecroIr2 selectively accumulates in mitochondria, leading to oxidative stress and loss of mitochondrial membrane potential (MMP). NecroIr2 activates receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like pseudokinase (MLKL), and regulates CDK4 expression.

NecroIr1 is an iridium(III) complex, serves as necroptosis inducers in Cisplatin (HY-17394)-resistant lung cancer cells (A549R). NecroIr1 selectively accumulates in mitochondria, leading to oxidative stress and loss of mitochondrial membrane potential (MMP). NecroIr1 activates receptor-interacting serine-threonine kinase 3 (RIPK3) and Mixed Lineage Kinase (MLKL), and regulates CDK4 expression.

Topoisomerase I/II Inhibitor 8 (Compound Ru7) is a dual catalytic inhibitor of Topoisomerase I/II, capable of inducing DNA damage and PARP-1 activation, which subsequently leads to the activation of RIPK1, RIPK3, and MLKL, ultimately triggering necroptosis. Topoisomerase I/II Inhibitor 8 demonstrates remarkable anticancer activity by effectively targeting the nuclei of cancer cells and inducing cell death through necroptosis, showing great clinical potential in circumventing drug resistance in cancer treatment.

VDX-111 is an analog of vitamin D. VDX-111 exhibits cytotoxicity in ovarian cancer cells through upregulation of RIPK1/RIPK3 pathway and induction of necroptosis. VDX-111 promotes expressions of cytokines and exhibits antitumor activity in mouse model.

Necroptosis inducer 2 is a necroptosis inducer and copper chelator. Necroptosis inducer 2 chelates intracellular free copper ions, disrupts redox homeostasis, elevates ROS levels, disrupts mitochondrial membrane potential, and induces cancer cell necroptosis. Necroptosis inducer 2 upregulates the necroptosis markers p-MLKL and p-RIP3 expression. Necroptosis inducer 2 exhibits anti-tumor activity in mice. Necroptosis inducer 2 can be used for the research of cancer, such as triple-negative breast cancer.

RIP3 activator 1 (compound C8) is a potent RIP3 activator. RIP3 activator 1 inhibits cell growth. RIP3 activator 1 induces necroptosis through the RIP3/p62/Keap1 signaling pathway. RIP3 activator 1 increases the protein expression of p-MLKL. RIP3 activator 1 induces autophagy. RIP3 activator 1 increases accumulation of LC3-II and p62 protein expression.

Anticancer agent 267 (Compound 5q) is the activator for RIPK3 and MLKL. Anticancer agent 267 inhibits the proliferation in a variety of cancer cell lines (IC₅₀ for MDA-MB-231, MDA-MB-486 and MCF-7 is 9.79, 10.77 and 5.94 μM, respectively), arrests cell cycle at subG1 phase, and induces necroptosis in cell MDA-MB-231. Anticancer agent 267 exhibits antitumor activity in mouse xenograft models.