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Clinical Combination Studies with Targeted Agents Clinical studies to-date have demonstrated feasibility of several targeted combination approaches, with a focus on inhibitors of EGFR and mTOR

1) Oxidative block irreversible, makes NADPH and CO Step 1: G6P + NADP 6-phosphogluconolactone + NADPH via G6PD (rate-limiting) Step 2: lactone + HO 6-phosphogluconate Step 3: 6-PG + NADP ribulose-5-P (Ru5P) + CO + NADPH Net per G6P: 2 NADPH + CO + Ru5P 2) Non-oxidative block reversible sugar shuffling Ru5P ribose-5-P (R5P) or xylulose-5-P (Xu5P) Transketolase (TPP-dependent) moves 2-carbon pieces: Xu5P + R5P sedoheptulose-7-P + GAP

These bioactive molecules can have therapeutic potential by influencing energy intake, in addition to reducing the proinflammatory state, oxidative stress and metabolic disorders (200)

Peer review Peer review information Nature Communications thanks Shaopeng Wang and the other, anonymous, reviewers for their contribution to the peer review of this work

MG-H1 formation in proteins leads to the substitution of charged hydrophilic arginine residue with hydrophobic uncharged MG-H1 residue

T., Thomas, G