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The negative charge that RSH to RSSH replacement introduces into this hydrophobic cavity due to the lower p K a of persulfide further affects the size of the cavity, hindering the interaction with additional phosphoinositide molecules (Aroca et al., 2021)

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Ferraro PM, Curhan GC, Gambaro G, Taylor EN

TD-1473 is an oral pan-JAK inhibitor designed to inhibit the JAK family of enzymes locally in the GI mucosa while minimizing systemic exposure through limited oral absorption and rapid systemic clearance