7DG

7DG (7-Desacetoxy-6,7-dehydrogedunin) is a PKR inhibitor, P2X7 purinergic receptor inhibitor, and skin-lightening agent. 7DG binds outside the ATP-catalytic domain of PKR, blocks the kinase activity-independent protein-protein interactions of PKR, inhibits the phosphorylation and activity of PKR, disrupts ASC assembly and caspase-1 activation, and suppresses the activation of the NLRP1 inflammasome. 7DG inhibits pyroptosis, suppresses the ATP-P2X7 signaling pathway, and abolishes ATP-induced increases in the expression levels of MITF, tyrosinase, PMEL/gp100, and melanin content. 7DG exerts skin-lightening effects in cultured skin in vitro. 7DG can be used in research related to chronic obstructive pulmonary disease, gout, type 2 diabetes, Alzheimer's disease, and hyperpigmentary skin disorders^[1][2][3]. IC50 & Target:protein kinase R (PKR)^[1] In Vitro:7DG (0.001-10 μM; administered within up to 1 h after LT exposure) reversibly protects J774 macrophages from lethal toxin (LT)-induced pyroptotic cell death, with an IC₅₀ of 5 μM, and remains active when added within 1 hour after LT exposure^[1].
7DG (10 μM, 2 h) inhibits LT-induced caspase-1 activation in J774 macrophages by targeting upstream steps of caspase-1 activation, without directly inhibiting the enzymatic activity of caspase-1^[1].
7DG (20 μM; 2 h) inhibits LPS (HY-D1056)-induced IκBβ degradation in J774 macrophages, and suppresses NLRP3 inflammasome-mediated caspase-1 activation in J774 macrophages treated with LPS + nigericin^[1].
7DG (1 h) inhibits the assembly of NLRP1 and NLRP3 inflammasomes in immortalized mouse macrophages with constitutive NLRP3 expression by targeting the kinase-independent function of PKR^[1].
7DG directly targets PKR in macrophages, inhibits PKR phosphorylation, and protects macrophages from LT-induced NLRP1 inflammasome-mediated pyroptosis^[2].
7DG (5.6-50 μM; 30 min) inhibits P2X7 activity in HOS-P2X7 cells^[3].
Incubation with 10 μM 7DG for 4 days (within the concentration range of 0.1-10 μM over 4 days) significantly reduces the viability of PHEM cells^[3].
7DG (0.5-2 μM; 1 h pre-incubation, followed by 3 days of co-treatment with 100 μM ATP) potently inhibits ATP (HY-B2176)-induced P2X7 activity in PHEMs^[3].
7DG (0.5-2 μM; 1 h pre-incubation followed by 72 h co-treatment with 100 μM ATP) inhibits ATP-induced melanogenesis in PHEMs by reducing the expression of melanogenesis-related proteins, tyrosinase activity, and melanin content^[3].
7DG (0.5-2 μM; 4-72 h) reduces melanogenesis in PHEMs without ATP stimulation^[3].
7DG (2 μM, daily for 9 consecutive days, with UVB irradiation supplemented on days 5 to 7) inhibits UVB-induced pigmentation in organ-cultured human skin after 9 days of treatment^[3].