VX-166 significantly improves survival in an endotoxic shock model in the mouse. Survival was monitored for 96 hours following administration of a lethal dose of lipopolysaccharide (LPS; 20 mg/kg iv) to male CD-1 mice (n = 28 per group). VX-166 was administered by repeat iv bolus at 0, 4, 8 and 12 hours following LPS. (a) Dose response of VX-166 dosed at 1 (triangles), 3 (empty circles), 10 (diamonds) or 30 mg/kg (squares) vs. vehicle control (full circles); *P < 0.01. (b) Single dose repeat study using the optimal dose (30 mg/kg) of VX-166 (squares) vs. vehicle control (circles); *P < 0.001. Survival in the vehicle group was different from (a) experiment due to a different batch of LPS used.