Inactivating warheads

Targanox goes after rare oxidized cysteines to access difficult protein targets

Targanox Inc. believes it has found a way to access some previously undruggable enzyme targets by taking advantage of changes in the oxidation state of cysteine residues to trap the enzymes in an inactive configuration.

Intracellular cysteine residues generally reside in a thiol (reduced) form, but can be modified by reactive oxygen species to reach a range of oxidation states. One common reaction is cysteine oxidation to sulfenic acid, a reversible posttranslational modification that can regulate protein behavior.

Reactive oxygen species have been associated with conditions like cancer, neurodegeneration and cardiovascular disease, but generally have been viewed as promiscuous

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