Characterization of KB-R7785. (A) Structure of KB-R7785: [4-(N-hydroxyamino)-2R-isobutyl-3S-methylsucciny1]-L-phenylglycine-N-methylamide. (B) Inhibition of TNF-α release from LPS-simulated THP-1. THP-1 cells were stimulated with 1 μg/mL LPS for 72 hours in the presence of the indicated dose of KB-R7785 (▴), KB-R8301 (▪), or KB-R8845 (•). TNF-α in the supernatants was measured by ELISA. Data are indicated as a percentage of control TNF-α release in the absence of inhibitors (112 ± 39 pg/mL) and are the mean ± SD of triplicate samples. (C) Inhibition of FasL release from hFasL/L5178Y. hFasL/L5178Y cells were cultured for 24 hours in the presence of the indicated doses of KB-R7785 (▴), KB-R8301 (▪), or KB-R8845 (•). FasL in the supernatants was measured by ELISA. Data are indicated as a percentage of control FasL release in the absence of inhibitors (13.9 ± 3.3 ng/mL) and are the mean ± SD of triplicate samples. (D) Prevention of lethal endotoxin shock. BALB/c mice received IP 30 mg/kg (▴) or 100 mg/kg (▪) of KB-R7785, 100 mg/kg of KB-R8301 (♦), or an equal volume of 0.5% CMC (•). After 1 hour, these mice were injected IV with 30 mg of D-galactosamine and 3 μg of LPS. The results are shown as a survival rate of 8 mice in each group at the indicated time points.