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Covalent/irreversible inhibitors target the redox/catalytic apparatus of TGR with almost no recognition elements that give affinity and selectivity for TGR over off-targets and the cellular redox apparatus resulting in undesirable cross-reactions and low specificity in vivo 25
The sub-30-minute plasma half-life is the pharmacokinetic basis for twice-daily dosing, though no human study has confirmed this produces better outcomes
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