Cited 4 times in
Novel allosteric glutaminase 1 inhibitors with macrocyclic structure activity relationship analysis
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 조병철 | - |
dc.date.accessioned | 2022-12-22T05:01:03Z | - |
dc.date.available | 2022-12-22T05:01:03Z | - |
dc.date.issued | 2022-11 | - |
dc.identifier.issn | 0960-894X | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/192277 | - |
dc.description.abstract | Glutamine-addicted cancer metabolism is recently recognized as novel cancer target especially for KRAS and KEAP1 co-occurring mutations. Selective glutaminase1 (GLS1) inhibition was reported using BPTES which has novel mode of allosteric inhibition. However, BPTES is a highly hydrophobic and symmetric molecule with very poor solubility which results in suboptimal pharmacokinetic parameters and hinders its further development. As an ongoing effort to identify more drug-like GLS1 inhibitors via systematic structure - activity relationship (SAR) analysis of BPTES analogs, we disclose our novel macrocycles for GLS1 inhibition with conclusive SAR analysis on the core, core linker, and wing linker, respectively. Selected molecules resulted in reduction in intracellular glutamate levels in LR (LDK378-resistant) cells which is consistent to cell viability result. Finally, compounds 13 selectively reduced the growth of A549 and H460 cells which have co-occurring mutations including KRAS and KEAP1. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Pergamon Press | - |
dc.relation.isPartOf | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Glutamates | - |
dc.subject.MESH | Glutaminase* | - |
dc.subject.MESH | Glutamine / metabolism | - |
dc.subject.MESH | Kelch-Like ECH-Associated Protein 1 / metabolism | - |
dc.subject.MESH | NF-E2-Related Factor 2 / metabolism | - |
dc.subject.MESH | Proto-Oncogene Proteins p21(ras) / metabolism | - |
dc.subject.MESH | Structure-Activity Relationship | - |
dc.subject.MESH | Sulfides / chemistry | - |
dc.subject.MESH | Thiadiazoles* / chemistry | - |
dc.title | Novel allosteric glutaminase 1 inhibitors with macrocyclic structure activity relationship analysis | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Eun Ji Lee | - |
dc.contributor.googleauthor | Krishna Babu Duggirala | - |
dc.contributor.googleauthor | Yujin Lee | - |
dc.contributor.googleauthor | Mi Ran Yun | - |
dc.contributor.googleauthor | Jiyoon Jang | - |
dc.contributor.googleauthor | Rajath Cyriac | - |
dc.contributor.googleauthor | Myoung Eun Jung | - |
dc.contributor.googleauthor | Gildon Choi | - |
dc.contributor.googleauthor | Chong Hak Chae | - |
dc.contributor.googleauthor | Byoung Chul Cho | - |
dc.contributor.googleauthor | Kwangho Lee | - |
dc.identifier.doi | 10.1016/j.bmcl.2022.128956 | - |
dc.contributor.localId | A03822 | - |
dc.relation.journalcode | J00326 | - |
dc.identifier.eissn | 1464-3405 | - |
dc.identifier.pmid | 36038117 | - |
dc.subject.keyword | Anticancer | - |
dc.subject.keyword | BPTES | - |
dc.subject.keyword | Cancer metabolism | - |
dc.subject.keyword | GLS1 | - |
dc.subject.keyword | Glutaminase 1 | - |
dc.subject.keyword | KEAP1 | - |
dc.subject.keyword | KRAS | - |
dc.subject.keyword | Macrocycle | - |
dc.contributor.alternativeName | Cho, Byoung Chul | - |
dc.contributor.affiliatedAuthor | 조병철 | - |
dc.citation.volume | 75 | - |
dc.citation.startPage | 128956 | - |
dc.identifier.bibliographicCitation | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, Vol.75 : 128956, 2022-11 | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.