PANoptosis Inhibitor

Melatonin is a hormone made by the pineal gland that can activate melatonin receptor and inhibit PANoptosis. Melatonin plays a role in sleep and possesses important antioxidative and anti-inflammatory properties. Melatonin is a novel selective ATF-6 inhibitor and induces human hepatoma cell apoptosis through COX-2 downregulation. Melatonin attenuates palmitic acid-induced (HY-N0830) mouse granulosa cells apoptosis via endoplasmic reticulum stress.

MNS (NSC 170724), the beta-nitrostyrene derivative, is an orally active tyrosine kinase inhibitor, a broad-spectrum antiplatelet agent, and a PANoptosis inhibitor. MNS inhibits Src, Syk, and FAK with IC₅₀ of 27.3, 2.8, and 97.6 μM, respectively. MNS inhibits NLRP3 inflammasome and β1 integrin. MNS completely inhibits U46619, ADP-, arachidonic acid-, collagen-, and thrombin-induced platelet aggregation with IC₅₀ values of 2.1, 4.1, 5.8, 7.0, and 12.7 μM, respectively. MNS is cytotoxic to a variety of cells.

TAT-N24 is a cell-penetrating peptide and also an inhibitor of p55PIK. TAT-N24 disrupts the interactions between p55PIK and p53, PCNA or Rb, blocks the p53-dependent ubiquitin-mediated degradation process, and inhibits the nuclear translocation and phosphorylation of NF-κB p65. TAT-N24 enhances MMS-induced p53-dependent cell apoptosis, inhibits DNA synthesis, reduces the expression of Cyclin D1, and induces cell cycle arrest at the G0/G1 or S phase. TAT-N24 inhibits the activation of NLRP3 and NLRC4 inflammasomes, reduces the expression of ZBP1-PANoptosome components, and suppresses PANoptosis. TAT-N24 can be used in research related to leukemia, colon cancer, cervical cancer, liver cancer, corneal neovascularization, restenosis and acute glaucoma.