3 91 0 ± 1 0 91 2 ± 1 1 91 4 ± 0 9 91 8 ± 0 9 91 9 ± 0 8 92 2 ± 0

3 91.0 ± 1.0 91.2 ± 1.1 91.4 ± 0.9 91.8 ± 0.9 91.9 ± 0.8 92.2 ± 0.8 92.1 #CA-4948 molecular weight randurls[1|1|,|CHEM1|]# ± 0.8 92.7 ± 0.7 StO2 end (%) Baseline 39.7 ± 3.5 44.8 ± 3.5 47.3 ± 4.2 47.3 ± 3.6 49.0 ± 3.0 49.7 ± 3.1 50.1 ± 2.7 47.8 ± 3.1 48.0 ± 2.8 48.0 ± 3.5 StO2 difference Baseline 45.5 ± 3.3 45.4 ± 3.4 43.7 ± 3.9 43.9 ± 3.5 42.4 ± 2.8 42.1 ± 2.8 41.8 ± 2.6 44.4 ± 2.9 44.1 ± 2.7 44.7 ± 3.3 StO2 start (%) Placebo 84.3 ± 1.3 91.0 ± 0.8 91.4 ± 0.8 91.8 ± 0.7 91.9 ± 0.8 92.3 ± 0.7 92.0 ± 0.7 92.2 ± 0.7 92.5 ± 0.6 92.5 ± 0.6 StO2 end (%) Placebo 39.2 ± 3.7 45.8 ± 4.2 48.8 ± 4.0 48.8 ± 4.5 50.1 ± 3.8 48.9 ± 4.3 49.0 ± 4.1 47.9 ± 4.1 50.1 ± 4.2 50.2 ± 4.0 StO2 difference Placebo 45.1 ± 3.5 45.2 ± 4.3 42.5 ± 4.2 43.0

± 4.6 41.2 ± 3.8 43.3 ± 4.3 42.9 ± 4.1 44.3 ± 4.0 42.5 ± 4.1 42.3 ± 3.9 StO2 start (%) GlycoCarn®* 84.5 ± 0.8 92.1 ± 0.5 92.5 ± 0.5 92.5 ± 0.4 93.0 ± 0.4 92.9 ± 0.4 93.1 ± 0.5 92.9 ± 0.4 93.0 ± 0.4 92.7 ± 0.5 StO2 end (%) GlycoCarn® 40.5 ± 3.7 45.3 ± 3.6 46.9 ± 4.7 49.1 ± 3.9 49.9 ± 3.8 51.5 ± 3.7 50.5 ± 3.7 52.5 ± 3.7 49.6 ± 4.0 50.4 ± 3.4 StO2 difference GlycoCarn® 44.0 ± 3.7 46.8 ± 3.4 45.6 ± 4.6 43.5 ± 3.8 41.1 ± 3.7 41.4 ± 3.7 42.6 ± 3.7 40.4 ± 3.6 43.3 ± 3.9 42.4 ± 3.4 StO2 start (%) SUPP1 83.6 ± 1.1 90.7 ± 0.8 91.3 ± 0.7 91.6 ± 0.6 91.8 ± 0.7 92.1 ± 0.6 92.7 ± 0.5 92.5 ± 0.6 92.4 ± 0.5 92.4 ± 0.5 StO2 end (%) SUPP1*** 38.4 ± 4.9 40.3 ± 4.6 40.7 ± 4.7 43.3 ± 4.7 42.8 ± 4.6 44.0 ± 4.4 46.2 ± 4.6 43.1 ± 4.7 43.8

± 4.8 45.3 ± 4.9 StO2 PI3K inhibitor difference SUPP1*** 45.2 ± 4.8 50.4 ± 4.9 50.6 ± 4.7 48.4 ± 4.7 48.9 ± 4.5 48.1 ± 4.3 46.5 ± 4.6 49.4 ±

4.6 48.5 ± 4.7 47.1 ± 4.8 StO2 start (%) SUPP2* 85.7 ± 1.3 90.1 ± 0.9 90.6 ± 0.8 91.4 ± 0.7 91.7 ± 0.7 91.6 ± 0.7 91.9 ± 0.7 92.5 ± 0.7 91.9 ± 0.7 92.5 ± 0.7 StO2 end (%) SUPP2 38.2 ± 3.5 44.3 ± 4.1 47.2 ± 4.2 47.5 ± 3.5 50.0 ± 3.7 49.6 ± 4.3 51.1 ± 4.1 50.4 ± 4.4 51.2 ± 3.8 53.6 ± 3.7 StO2 difference SUPP2 47.5 ± 3.3 45.8 ± 3.8 43.4 ± 3.9 43.9 ± 3.4 41.7 ± 3.5 42.1 ± 4.1 40.9 ± 3.8 42.1 ± 4.0 40.8 ± 3.6 38.9 ± 3.4 StO2 start (%) SUPP3 84.2 ± 1.1 90.8 ± 0.9 91.1 ± 0.9 91.6 ± 0.8 91.7 ± 0.7 91.9 ± 0.7 92.0 ± 0.6 92.1 ± 0.6 92.4 ± 0.6 92.9 ± 0.6 StO2 end (%) SUPP3 42.9 ± 4.2 47.1 ± 4.1 47.9 ± 3.7 50.9 ± 4.0 47.9 ± 3.3 49.7 ± 3.6 49.5 ± 3.9 51.3 ± 3.9 51.0 ± 4.0 51.1 ± 4.0 StO2 difference SUPP3 41.2 ± 3.8 43.7 ± 3.9 Protein kinase N1 43.2 ± 3.5 40.7 ± 3.7 43.8 ± 3.2 42.2 ± 3.4 42.6 ± 3.7 40.8 ± 3.7 41.4 ± 3.8 41.8 ± 3.7 Data are mean ± SEM.

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