Cisd2 agonist 2 (compound 6) is a Cisd2 activator (EC50=191 nM), and Cisd2 levels are associated with non-alcoholic fatty liver disease (NAFLD). Cisd2 agonist 2 has no significant in vivo toxicity in Cisd2hKO-het mice (heterozygous hepatocyte-specific Cisd2 knockout). Cisd2 (CDGSH iron sulfur domain 2) is a zinc finger protein that is mainly localized in the endoplasmic reticulum or mitochondrial membrane. Cisd2 participates in mitochondrial function by forming homodimers containing two redox-active 2Fe-2S clusters[1][2].
References
[1] Yao CH, et al. Discovery of tetrasubstituted thiophenes as Cisd2 activators: A potential novel therapeutic option in nonalcoholic fatty liver disease. Eur J Med Chem. 2023 Oct 5;258:115583. DOI:10.1016/j.ejmech.2023.115583 [2] Li J, et al. CDGSH Iron Sulfur Domain 2 Deficiency Inhibits Cell Proliferation and Induces Cell Differentiation of Neuroblastoma. Pathol Oncol Res. 2020 Jul;26(3):1725-1733. DOI:10.1007/s12253-019-00753-7
