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Moreover, the magnitude of WL with retatrutide also exceeded that seen with other pipeline multi-agonists such as CagriSema (cagrilintide, an amylin agonist, in combination with semaglutide), mazdutide and survodutide (Fig

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Additionally, the pocket normally occupied by the conserved phenylalanine residue of the TIN2 F-X-L-X-P motif was fully obstructed by a crystal contact with a TRF1 TRFH copy in an adjacent asymmetric unit, further limiting the possibility of obtaining XChem hits outside of the leucine pocket

Hence, Cd would greatly lower lysosomal pH (Fig