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- W2912933215 abstract "The gut hormone PYY3-36 reduces food intake in humans and exhibits at least additive efficacy in combination with GLP-1. However, the utility of PYY analogs as anti-obesity agents has been severely limited by emesis and rapid proteolysis, a profile similarly observed with native PYY3-36 in obese rhesus macaques. Here, we found that antibody conjugation of a cyclized PYY3-36 analog achieved high NPY2R selectivity, unprecedented in vivo stability, and gradual infusion-like exposure. These properties permitted profound reduction of food intake when administered to macaques for 23 days without a single emetic event in any animal. Co-administration with the GLP-1 receptor agonist liraglutide for an additional 5 days further reduced food intake with only one animal experiencing a single bout of emesis. This antibody-conjugated PYY analog therefore may enable the long-sought potential of GLP-1/PYY-based combination treatment to achieve robust, well-tolerated weight reduction in obese patients." @default.
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- W2912933215 date "2019-04-01" @default.
- W2912933215 modified "2023-10-11" @default.
- W2912933215 title "A Long-Acting PYY3–36 Analog Mediates Robust Anorectic Efficacy with Minimal Emesis in Nonhuman Primates" @default.
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- W2912933215 doi "https://doi.org/10.1016/j.cmet.2019.01.017" @default.
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