Compound 3 in anti-CD3 mouse model. (A) pS6RP
levels
(normalized to total S6RP) measured in spleens of compound treated
as compared to disease vehicle group (p < 0.01
for 1 mg/kg of 3; p < 0.001 for 3
and 10 mg/kg of 3; one outlier removed in normal control
and disease vehicle group). (B) Exposure response fit: pS6RP levels
at terminal exposure. EC50 0.22 μM (95% CI 0.15 to
0.32 μM). (C) pAkt levels (normalized to total Akt) measured
in spleens of compound treated as compared to disease vehicle group
(p < 0.001 for 1, 3, and 10 mg/kg of 3). (D) Exposure response fit: pAkt levels at terminal exposure. EC50 0.055 μM (95% CI 0.048 to 0.065 μM). Legend:
White, normal controls (n = 4). Black, anti-CD3 vehicle
5%DMSO/95% (10% kleptose) (n = 6). Gray, anti-CD3/3 (1, 3, or 10 mg/kg, of 3 PO) (n = 6).