title: Casitas B-Lineage Lymphoma RING Domain Inhibitors Protect Mice against High-Fat Diet-Induced Obesity and Insulin Resistance.
abstract: The casitas b-lineage lymphoma (c-Cbl) is an important adaptor protein with an intrinsic E3 ubiquitin ligase activity that interacts with E2 proteins such as UbCH7. c-Cbl plays a vital role in regulating receptor tyrosine kinase signaling. c-Cbl involves in whole-body energy homeostasis, which makes it a potential target for the treatment of type 2 diabetes and obesity. In the present study, we have designed two parental peptides and 55 modified peptides based on the structure of UbCH7 loop L1 and L2. Thirteen of the modified peptides showed increased inhibitory activity in a fluorescence polarization-based assay. In the in vivo proof of study principle, mice treated with peptides 10, 34, 49 and 51 were protected against high-fat diet-induced obesity and insulin resistant. These inhibitors may potentially lead to new therapeutic alternatives for obesity and type 2 diabetes.
authors: Department of Pharmacy, Chengdu Medical College. Chengdu, Sichuan Province, China.
authors: Min
authors: M
authors: Wu
authors: West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors: Lin
authors: L
authors: Sun
authors: Department of Pathology and Laboratory Medicine, Univerisity of Kansas Medical Center, Kansas City, KS, United States of America.
authors: Ziyan Yuan
authors: ZY
authors: Pessetto
authors: Department of Pharmacy, Chengdu Medical College. Chengdu, Sichuan Province, China.
authors: Zhihe
authors: Z
authors: Zang
authors: Department of Pharmacy, Chengdu Medical College. Chengdu, Sichuan Province, China.
authors: Xingliang
authors: X
authors: Xie
authors: Department of Pharmacy, Chengdu Medical College. Chengdu, Sichuan Province, China.
authors: Ling
authors: L
authors: Zhong
authors: Department of Pharmacy, Chengdu Medical College. Chengdu, Sichuan Province, China.
authors: Qing
authors: Q
authors: Su
authors: Department of Pharmacy, Chengdu Medical College. Chengdu, Sichuan Province, China.
authors: Wang
authors: W
authors: Zan
authors: Department of Pharmacy, Chengdu Medical College. Chengdu, Sichuan Province, China.
authors: Xiurong
authors: X
authors: Gao
authors: Department of Pharmacy, Chengdu Medical College. Chengdu, Sichuan Province, China.
authors: Yan
authors: Y
authors: Zhao
authors: Department of Pharmacy, Chengdu Medical College. Chengdu, Sichuan Province, China.
authors: Yiyi
authors: Y
authors: Sun
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004734:Energy Metabolism / Q000187:drug effects; D015870:Gene Expression; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D050721:Proto-Oncogene Proteins c-cbl / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D019440:Anti-Obesity Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D011994:Recombinant Proteins; D050721:Proto-Oncogene Proteins c-cbl; C493849:Cbl protein, mouse