In vivo efficacy of PF-3644022 in rat acute and chronic inflammation models

LPS-induced TNFα production ED50/80 and EC50/80 values from the rat acute model were calculated from data shown in Fig. 5 A and B, respectively. ED50/80 and EC50/80 parameters from the rat SCW-induced arthritis model were determined by using data from Fig. 6 A and B, respectively.

Acute LPS-induced TNFα production
    ED50/ED80 (mg/kg)6.9/19
    EC50/EC80 (C5.5 h; μM)1.4/4.2
    EC50/EC80 ffa (C5.5 h; mM)0.11/0.34
Chronic SCW-induced arthritis
    ED50/ED80 (mg/kg, b.i.d.)20/50–100b
    EC50/EC80 (Cmax; μM)11/28–51b
    EC50/EC80 (Cmin; μM)0.91/4.9–13.5b
    EC50/EC80 (AUC; μM×h)34/117–248b
  • a Free fraction concentrations of PF-3644022 were calculated from a measured PF-3644022 rat plasma protein value of 92.1%.

  • b Efficacy values at 80% inhibition are approximate because of maximum efficacy of 75 to 82% observed with MK2 inhibitors in the rat SCW model.