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Pro3GIP(3-30)Cex-K40[Pal] is a synthetic peptide **GIP receptor antagonist** engineered for enhanced metabolic stability and extended half-life. It is based on the native peptide GIP(3–30), with a Pro^3^ substitution, a nine-residue exendin-4 C-terminal extension (Cex), and a C-terminal lysine at position 40 modified with a C-16 palmitoyl (Pal) fatty acid. These modifications reduce renal clearance and preserve receptor antagonism. Pro3GIP(3-30)Cex-K40[Pal] potently inhibits **glucose-dependent insulinotropic polypeptide receptor (GIPR)** signaling, blocking GIP-induced cAMP recruitment and insulin secretion in rodent and cell-based models. In preclinical studies, it induces **weight loss, improves glycemic control, and counteracts insulin resistance** in diet-induced obese mice with minimal effect on lean mass. The molecule was primarily developed for experimental use in obesity and diabetes research. The modifications aim to optimize pharmacokinetics for in vivo use[1][7].
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