Discovery of a Novel Class of Diacylglycerol Acyltransferase 2 Inhibitors with a 1H-Pyrrolo[2,3-b]pyridine Core
DC Field | Value | Language |
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dc.contributor.author | Kim, Mun Ock | - |
dc.contributor.author | Lee, Suui | - |
dc.contributor.author | Choi, Kwangman | - |
dc.contributor.author | Lee, Sangku | - |
dc.contributor.author | Kim, Hyeongki | - |
dc.contributor.author | Kang, Hyunju | - |
dc.contributor.author | Choi, Miri | - |
dc.contributor.author | Kwon, Eun Bin | - |
dc.contributor.author | Kang, Myung Ji | - |
dc.contributor.author | Kim, Sunhong | - |
dc.contributor.author | Lee, Hyun-Jun | - |
dc.contributor.author | Lee, Hyun Sun | - |
dc.contributor.author | Kwak, Young-Shin | - |
dc.contributor.author | Cho, Sungchan | - |
dc.date.accessioned | 2021-09-05T04:56:05Z | - |
dc.date.available | 2021-09-05T04:56:05Z | - |
dc.date.created | 2021-06-15 | - |
dc.date.issued | 2014-10 | - |
dc.identifier.issn | 0918-6158 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/97345 | - |
dc.description.abstract | Diacylglycerol acyltransferase 2 (DGAT2), which catalyzes the final step in triacylglycerol (TG) synthesis, is a key enzyme associated with hepatic steatosis and insulin resistance. Here, using an in vitro screen of 20000 molecules, we identified a class of compounds with a substituted 1H-pyrrolo[2,3-b]pyridine core which proved to be potent and selective inhibitors of human DGAT2. Of these compounds, H2-003 and -005 exhibited a considerable reduction in TG biosynthesis in HepG2 hepatic cells and 3T3-L1 preadipose cells. These compounds exert DGAT2-specific-inhibitory activity, which was further confirmed in DGAT2- or DGAT1-overexpressing HEK293 cells. In addition, these compounds almost completely abolished lipid droplet formation in 3T3-L1 cells when co-treated with a DGAT1 inhibitor, which was not attained using either a DGAT2 or DGAT1 inhibitor alone. Collectively, we identified two DGAT2 inhibitors, H2-003 and -005. These compounds will aid in DGAT2-related lipid metabolism research as well as in therapeutic development for the treatment of metabolic diseases associated with excessive TG. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | PHARMACEUTICAL SOC JAPAN | - |
dc.subject | INSULIN-RESISTANCE | - |
dc.subject | TRIGLYCERIDE SYNTHESIS | - |
dc.subject | HEPATIC STEATOSIS | - |
dc.subject | MICE | - |
dc.subject | ACCUMULATION | - |
dc.subject | OBESITY | - |
dc.subject | DGAT1 | - |
dc.subject | OVEREXPRESSION | - |
dc.subject | BIOSYNTHESIS | - |
dc.subject | SUPPRESSION | - |
dc.title | Discovery of a Novel Class of Diacylglycerol Acyltransferase 2 Inhibitors with a 1H-Pyrrolo[2,3-b]pyridine Core | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kwak, Young-Shin | - |
dc.identifier.doi | 10.1248/bpb.b14-00447 | - |
dc.identifier.scopusid | 2-s2.0-84908052356 | - |
dc.identifier.wosid | 000342479800011 | - |
dc.identifier.bibliographicCitation | BIOLOGICAL & PHARMACEUTICAL BULLETIN, v.37, no.10, pp.1655 - 1660 | - |
dc.relation.isPartOf | BIOLOGICAL & PHARMACEUTICAL BULLETIN | - |
dc.citation.title | BIOLOGICAL & PHARMACEUTICAL BULLETIN | - |
dc.citation.volume | 37 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 1655 | - |
dc.citation.endPage | 1660 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | INSULIN-RESISTANCE | - |
dc.subject.keywordPlus | TRIGLYCERIDE SYNTHESIS | - |
dc.subject.keywordPlus | HEPATIC STEATOSIS | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordPlus | ACCUMULATION | - |
dc.subject.keywordPlus | OBESITY | - |
dc.subject.keywordPlus | DGAT1 | - |
dc.subject.keywordPlus | OVEREXPRESSION | - |
dc.subject.keywordPlus | BIOSYNTHESIS | - |
dc.subject.keywordPlus | SUPPRESSION | - |
dc.subject.keywordAuthor | metabolic disease | - |
dc.subject.keywordAuthor | triacylglycerol | - |
dc.subject.keywordAuthor | diacylglycerol acyltransferase 2 (DGAT2) | - |
dc.subject.keywordAuthor | small molecule inhibitor | - |
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