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As noted, a phase 2 trial of retatrutide reported about 24% average body weight reduction in 48 weeks on the highest dose

10.1021/acs.jmedchem.6b01031 67 KramrE

Functioning independently of its canonical unfolded protein response role, the endoplasmic reticulum-resident protein IRE1 governs ferroptotic susceptibility through an evolutionarily conserved mechanism wherein its endoribonuclease activity degrades transcripts encoding glutathione biosynthesis factors GCLC and SLC7A11, rendering IRE1-deficient cells resistant while overexpressing cells hyper-sensitive to this death pathway (55)

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Replacement of Lys105 by uncharged residues in K105A/Y resulted in a 6597% decrease of the k cat app values for GSSCys and GSH (Fig