Cited 6 time in webofscience Cited 9 time in scopus

Selective novel inverse agonists for human GPR43 augment GLP-1 secretion

Selective novel inverse agonists for human GPR43 augment GLP-1 secretion
Park, BO[Park, Bi-Oh]Kim, SH[Kim, Seong Heon]Kong, GY[Kong, Gye Yeong]Kim, DH[Kim, Da Hui]Kwon, MS[Kwon, Mi So]Lee, SU[Lee, Su Ui]Kim, MO[Kim, Mun-Ock]Cho, S[Cho, Sungchan]Lee, S[Lee, Sangku]Lee, HJ[Lee, Hyun-Jun]Han, SB[Han, Sang-Bae]Kwak, YS[Kwak, Young Shin]Lee, SB[Lee, Sung Bae]Kim, S[Kim, Sunhong]
DGIST Authors
Lee, SB[Lee, Sung Bae]
Issue Date
European Journal of Pharmacology, 771, 1-9
Article Type
Agents Interacting With Transmitter, Hormone or Drug ReceptorsBTI-A-202BTI-A-292BTI-A-404Calcium IonCompetitive InhibitionControlled StudyCyclic AMPCytoplasmDrug IdentificationDrug PotencyDrug ScreeningDrug SelectivityDrug StructureG Protein-Coupled ReceptorGLP-1Glucagon Like Peptide 1GPR43High Throughput ScreeningImmunoglobulin Enhancer Binding ProteinInverse AgonistMitogen-Activated Protein KinaseMitogen-Activated Protein Kinase P38Priority JournalProtein GPR43Protein SecretionSCFASignal TransductionStructure Activity RelationUnclassified Drug
GPR43/Free Fatty Acid Receptor 2 (FFAR2) is known to be activated by short-chain fatty acids and be coupled to Gi and Gq family of heterotrimeric G proteins. GPR43 is mainly expressed in neutrophils, adipocytes and enteroendocrine cells, implicated to be involved in inflammation, obesity and type 2 diabetes. However, several groups have reported the contradictory data about the physiological functions of GPR43, so that its roles in vivo remain unclear. Here, we demonstrate that a novel compound of pyrimidinecarboxamide class named as BTI-A-404 is a selective and potent competitive inverse agonist of human GPR43, but not the murine ortholog. Through structure-activity relationship (SAR), we also found active compound named as BTI-A-292. These regulators increased the cyclic AMP level and reduced acetate-induced cytoplasmic Ca2+ level. Furthermore, we show that they modulated the downstream signaling pathways of GPR43, such as ERK, p38 MAPK, and NF-κB. It was surprising that two compounds augmented the secretion of glucagon-like peptide 1 (GLP-1) in NCI-H716 cell line. Collectively, these novel and specific competitive inhibitors regulate all aspects of GPR43 signaling and the results underscore the therapeutic potential of them. © 2015 Elsevier B.V. All rights reserved.
Elsevier B.V.
Related Researcher
  • Author Lee, Sung Bae SB LAB(Lab of Neurodegenerative diseases and Aging)
  • Research Interests Cellular mechanism of neurodegenerative diseases; Neuronal maintenance and remodeling; 퇴행성 뇌질환의 세포기전; 신경계 유지 및 리모델링 연구
There are no files associated with this item.
Department of Brain and Cognitive SciencesSB LAB(Lab of Neurodegenerative diseases and Aging)1. Journal Articles

qrcode mendeley

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.