This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt and/or hydrate and/or prodrug of the compound) that modulate (e.g., agonize or partially agonize or antagonize) glucagon‐like peptide‐1 receptor (“GLP‐1R”) and/or the gastric inhibitory polypeptide receptor (“GIPR”). The chemical entities are useful, e.g., for treating a subject (e.g., a human) having a disease, disorder, or condition in which modulation (e.g., agonism, partial agonism or antagonism) of GLP‐1R and/or GIPR activities is benficial for the treatment or prevention of the underlying pathology and/or symptoms and/or progression of the disease, disorder, or condition. In some embodiments, the modulation results in an enhancment of (e.g., an increase in) existing levels (e.g., normal or below normal levels) of GLP‐1R and/or GIPR activity (e.g., signaling). In some embodiments, the chemical entities described herein further modulate (e.g., attenuate, uncouple) β-arrestin signaling relative to what is observed with the native ligand. This disclosure also features compositions as well as other methods of using and making the said chemical entities.本發明提供化學實體(例如化合物或化合物的醫藥學上可接受的鹽及/或水合物及/或前藥)，其調節(例如促效或部分促效或拮抗)升糖素樣肽-1受體(「GLP-1R」)及/或抑胃多肽受體(「GIPR」)。該等化學實體適用於例如治療患有疾病、病症或病狀的個體(例如人類)，其中GLP-1R及/或GIPR活性的調節(例如促效作用、部分促效作用或拮抗作用)有益於治療或預防疾病、病症或病狀的潛在病理及/或症狀及/或進展。在一些實施例中，該調節導致GLP-1R及/或GIPR活性(例如信號傳導)的現有水準(例如正常或低於正常水準)的增強(例如增加)。在一些實施例中，本文所述之化學實體相對於天然配位體所觀測的進一步調節(例如減弱、解偶聯)β-抑制蛋白(arrestin)信號傳導。本發明亦提供組合物以及使用及製造該等化學實體的其他方法。
