Peptidomimetic‐based identification of FDA‐approved compounds inhibiting IRE1 activity
Inositol‐requiring enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Tumour cells experience ER stress due to adverse environmental cues such as hypoxia or nutrient...
Saved in:
Published in | The FEBS journal Vol. 288; no. 3; pp. 945 - 960 |
---|---|
Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Blackwell Publishing Ltd
01.02.2021
Wiley |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Inositol‐requiring enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Tumour cells experience ER stress due to adverse environmental cues such as hypoxia or nutrient shortage and high metabolic/protein‐folding demand. To cope with those stresses, cancer cells utilise IRE1 signalling as an adaptive mechanism. Here, we report the discovery of the FDA‐approved compounds methotrexate, cefoperazone, folinic acid and fludarabine phosphate as IRE1 inhibitors. These were identified through a structural exploration of the IRE1 kinase domain using IRE1 peptide fragment docking and further optimisation and pharmacophore development. The inhibitors were verified to have an impact on IRE1 activity in vitro and were tested for their ability to sensitise human cell models of glioblastoma multiforme (GBM) to chemotherapy. We show that all molecules identified sensitise glioblastoma cells to the standard‐of‐care chemotherapy temozolomide (TMZ).
FDA‐approved drugs and small peptides were identified as potent IRE1 inhibitors through a systematic in silico and in vitro exploration. The compounds block XBP1 mRNA splicing by IRE1 in vitro and at subtoxic doses sensitise glioblastoma cells to chemotherapy. The findings provide insights on utilising the inhibition of the unfolded protein response (UPR) as a modality in cancer treatment. |
---|---|
AbstractList | Inositol‐requiring enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Tumour cells experience ER stress due to adverse environmental cues such as hypoxia or nutrient shortage and high metabolic/protein‐folding demand. To cope with those stresses, cancer cells utilise IRE1 signalling as an adaptive mechanism. Here, we report the discovery of the FDA‐approved compounds methotrexate, cefoperazone, folinic acid and fludarabine phosphate as IRE1 inhibitors. These were identified through a structural exploration of the IRE1 kinase domain using IRE1 peptide fragment docking and further optimisation and pharmacophore development. The inhibitors were verified to have an impact on IRE1 activity in vitro and were tested for their ability to sensitise human cell models of glioblastoma multiforme (GBM) to chemotherapy. We show that all molecules identified sensitise glioblastoma cells to the standard‐of‐care chemotherapy temozolomide (TMZ).
FDA‐approved drugs and small peptides were identified as potent IRE1 inhibitors through a systematic in silico and in vitro exploration. The compounds block XBP1 mRNA splicing by IRE1 in vitro and at subtoxic doses sensitise glioblastoma cells to chemotherapy. The findings provide insights on utilising the inhibition of the unfolded protein response (UPR) as a modality in cancer treatment. Inositol-requiring enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Tumour cells experience ER stress due to adverse environmental cues such as hypoxia or nutrient shortage and high metabolic/protein-folding demand. To cope with those stresses, cancer cells utilise IRE1 signalling as an adaptive mechanism. Here, we report the discovery of the FDA-approved compounds methotrexate, cefoperazone, folinic acid and fludarabine phosphate as IRE1 inhibitors. These were identified through a structural exploration of the IRE1 kinase domain using IRE1 peptide fragment docking and further optimisation and pharmacophore development. The inhibitors were verified to have an impact on IRE1 activityin vitroand were tested for their ability to sensitise human cell models of glioblastoma multiforme (GBM) to chemotherapy. We show that all molecules identified sensitise glioblastoma cells to the standard-of-care chemotherapy temozolomide (TMZ). Inositol Requiring Enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of the Unfolded Protein Response (UPR) during endoplasmic reticulum (ER) stress. Tumour cells experience ER stress due to adverse environmental cues such as hypoxia or nutrient shortage and high metabolic/protein folding demand. To cope with those stresses, cancer cells utilise IRE1 signalling as an adaptive mechanism. Here we report the discovery of the FDA approved compounds methotrexate, cefoperazone, folinic acid and fludarabine phosphate as IRE1 inhibitors. These were identified through a structural exploration of the IRE1 kinase domain using IRE1 peptide fragment docking and further optimization and pharmacophore development. The inhibitors were verified to have an impact on IRE1 activity in vitro and were tested for their ability to sensitise human cell models of glioblastoma multiforme (GBM) to chemotherapy. We show that all molecules identified sensitise glioblastoma cells to the standard of care chemotherapy temozolomide (TMZ). Inositol‐requiring enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Tumour cells experience ER stress due to adverse environmental cues such as hypoxia or nutrient shortage and high metabolic/protein‐folding demand. To cope with those stresses, cancer cells utilise IRE1 signalling as an adaptive mechanism. Here, we report the discovery of the FDA‐approved compounds methotrexate, cefoperazone, folinic acid and fludarabine phosphate as IRE1 inhibitors. These were identified through a structural exploration of the IRE1 kinase domain using IRE1 peptide fragment docking and further optimisation and pharmacophore development. The inhibitors were verified to have an impact on IRE1 activity in vitro and were tested for their ability to sensitise human cell models of glioblastoma multiforme (GBM) to chemotherapy. We show that all molecules identified sensitise glioblastoma cells to the standard‐of‐care chemotherapy temozolomide (TMZ). Inositol‐requiring enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Tumour cells experience ER stress due to adverse environmental cues such as hypoxia or nutrient shortage and high metabolic/protein‐folding demand. To cope with those stresses, cancer cells utilise IRE1 signalling as an adaptive mechanism. Here, we report the discovery of the FDA‐approved compounds methotrexate, cefoperazone, folinic acid and fludarabine phosphate as IRE1 inhibitors. These were identified through a structural exploration of the IRE1 kinase domain using IRE1 peptide fragment docking and further optimisation and pharmacophore development. The inhibitors were verified to have an impact on IRE1 activity in vitro and were tested for their ability to sensitise human cell models of glioblastoma multiforme (GBM) to chemotherapy. We show that all molecules identified sensitise glioblastoma cells to the standard‐of‐care chemotherapy temozolomide (TMZ). Inositol-requiring enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Tumour cells experience ER stress due to adverse environmental cues such as hypoxia or nutrient shortage and high metabolic/protein-folding demand. To cope with those stresses, cancer cells utilise IRE1 signalling as an adaptive mechanism. Here, we report the discovery of the FDA-approved compounds methotrexate, cefoperazone, folinic acid and fludarabine phosphate as IRE1 inhibitors. These were identified through a structural exploration of the IRE1 kinase domain using IRE1 peptide fragment docking and further optimisation and pharmacophore development. The inhibitors were verified to have an impact on IRE1 activity in vitro and were tested for their ability to sensitise human cell models of glioblastoma multiforme (GBM) to chemotherapy. We show that all molecules identified sensitise glioblastoma cells to the standard-of-care chemotherapy temozolomide (TMZ). |
Author | Doultsinos, Dimitrios Paton, Adrienne W. Eriksson, Leif A. Paton, James C. Carlesso, Antonio Samali, Afshin Chevet, Eric Chintha, Chetan |
Author_xml | – sequence: 1 givenname: Dimitrios orcidid: 0000-0003-0873-9873 surname: Doultsinos fullname: Doultsinos, Dimitrios organization: Centre de Lutte contre le Cancer Eugène Marquis – sequence: 2 givenname: Antonio orcidid: 0000-0002-8318-7784 surname: Carlesso fullname: Carlesso, Antonio organization: University of Gothenburg – sequence: 3 givenname: Chetan orcidid: 0000-0002-0105-8066 surname: Chintha fullname: Chintha, Chetan organization: NUI Galway – sequence: 4 givenname: James C. orcidid: 0000-0001-9807-5278 surname: Paton fullname: Paton, James C. organization: University of Adelaide – sequence: 5 givenname: Adrienne W. orcidid: 0000-0002-2996-5733 surname: Paton fullname: Paton, Adrienne W. organization: University of Adelaide – sequence: 6 givenname: Afshin orcidid: 0000-0002-8610-8375 surname: Samali fullname: Samali, Afshin organization: NUI Galway – sequence: 7 givenname: Eric orcidid: 0000-0001-5855-4522 surname: Chevet fullname: Chevet, Eric email: eric.chevet@inserm.fr organization: Centre de Lutte contre le Cancer Eugène Marquis – sequence: 8 givenname: Leif A. orcidid: 0000-0001-5654-3109 surname: Eriksson fullname: Eriksson, Leif A. email: leif.eriksson@chem.gu.se organization: University of Gothenburg |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32446294$$D View this record in MEDLINE/PubMed https://univ-rennes.hal.science/hal-02862262$$DView record in HAL https://gup.ub.gu.se/publication/294294$$DView record from Swedish Publication Index |
BookMark | eNp90c2KFDEQAOAgK-6PXnwAafCiQq_pJJPpPo7rjLswoPgD4iWkk8pslu6kt9M9y9x8BJ_RJ7HGXgf0YAgkqXwUVdQpOQoxACFPC3pe4HrtoE7nxYzP2QNyUswFy4WclUeHu_h6TE5TuqGUz0RVPSLHnAkhWSVOyLcP0A3exta3MHjz8_uPWiewmbcQBu-80YOPIYsuW71d4K_uuj5uEZjYdnEMNmU-XPvaDz5ssquPyyLTZvBbP-wek4dONwme3J9n5Mtq-fniMl-_f3d1sVjnBstkOQjJJWNUC-54KawphOV6XlF8Vk5KazDIhTCm5k7WrpaVoJUFoYFq4IyfkXzKm-6gG2vV9b7V_U5F7dVm7BSGNqNKoLBh3OhfTv5aN3_hy8Va7WOUlViQZNsC7YvJYte3I6RBtT4ZaBodII5JMUElp3NW7unzf-hNHPuAnaMqBWO8khzVq0mZPqbUgztUUFC1n6baT1P9nibiZ_cpx7oFe6B_xoegmMCdb2D3n1RqtXzzaUr6C4LjrPw |
CitedBy_id | crossref_primary_10_1007_s12079_023_00784_5 crossref_primary_10_1007_s11010_022_04584_0 crossref_primary_10_1016_j_bbcan_2022_188839 crossref_primary_10_1016_j_ydbio_2022_09_009 crossref_primary_10_1016_j_isci_2023_106687 crossref_primary_10_1038_s42004_023_01092_0 crossref_primary_10_1016_j_csbj_2022_03_029 crossref_primary_10_1016_j_bbcan_2023_189054 crossref_primary_10_1042_BCJ20200919 crossref_primary_10_1002_ddr_22075 crossref_primary_10_1111_febs_16747 crossref_primary_10_1016_j_crmicr_2022_100119 crossref_primary_10_3390_biomedicines9020156 crossref_primary_10_1016_j_pupt_2023_102218 crossref_primary_10_14336_AD_2022_0824 |
Cites_doi | 10.15252/emmm.201404509 10.1016/j.molcel.2010.04.001 10.1111/febs.14608 10.1177/2472555217701685 10.1002/jcc.20084 10.1038/nchembio.1094 10.18632/oncotarget.5827 10.1021/ja00214a001 10.1136/ard.60.8.729 10.1016/j.cell.2018.10.049 10.1038/emboj.2011.18 10.1101/841296 10.1038/35014014 10.1021/ml500315b 10.1093/clinids/5.Supplement_1.S108 10.1158/1078-0432.CCR-17-1549 10.1038/s41467-018-05763-8 10.1038/nature05124 10.1038/nrd3976 10.1084/jem.20040392 10.1096/fj.11-182931 10.1038/ncomms5202 10.1186/1471-2105-7-11 10.1073/pnas.1115623109 10.1021/acschembio.5b00940 10.1111/j.1462-5822.2008.01164.x 10.1056/NEJM194806032382301 10.15252/emmm.201707929 10.1172/JCI95873 10.1002/art.1780360609 10.1021/jm030644s 10.1182/blood.V74.1.19.bloodjournal74119 10.1021/jm051256o 10.1177/1087057110363823 10.1111/febs.15107 10.18632/oncotarget.2051 10.1038/nature07428 10.1021/acs.jcim.5b00559 |
ContentType | Journal Article |
Copyright | 2020 The Authors. published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. 2020. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Attribution |
Copyright_xml | – notice: 2020 The Authors. published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies – notice: 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. – notice: 2020. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: Attribution |
DBID | 24P WIN NPM AAYXX CITATION 7QL 7QP 7QR 7TK 7TM 7U9 8FD C1K FR3 H94 M7N P64 RC3 7X8 1XC VOOES ADTPV AOWAS F1U |
DOI | 10.1111/febs.15372 |
DatabaseName | Wiley Online Library Open Access Wiley-Blackwell Free Backfiles(OpenAccess) PubMed CrossRef Bacteriology Abstracts (Microbiology B) Calcium & Calcified Tissue Abstracts Chemoreception Abstracts Neurosciences Abstracts Nucleic Acids Abstracts Virology and AIDS Abstracts Technology Research Database Environmental Sciences and Pollution Management Engineering Research Database AIDS and Cancer Research Abstracts Algology Mycology and Protozoology Abstracts (Microbiology C) Biotechnology and BioEngineering Abstracts Genetics Abstracts MEDLINE - Academic Hyper Article en Ligne (HAL) Hyper Article en Ligne (HAL) (Open Access) SwePub SwePub Articles SWEPUB Göteborgs universitet |
DatabaseTitle | PubMed CrossRef Virology and AIDS Abstracts Technology Research Database Nucleic Acids Abstracts Neurosciences Abstracts Biotechnology and BioEngineering Abstracts Environmental Sciences and Pollution Management Genetics Abstracts Bacteriology Abstracts (Microbiology B) Algology Mycology and Protozoology Abstracts (Microbiology C) AIDS and Cancer Research Abstracts Chemoreception Abstracts Engineering Research Database Calcium & Calcified Tissue Abstracts MEDLINE - Academic |
DatabaseTitleList | Virology and AIDS Abstracts CrossRef PubMed |
Database_xml | – sequence: 1 dbid: 24P name: Wiley_OA刊 url: https://authorservices.wiley.com/open-science/open-access/browse-journals.html sourceTypes: Publisher – sequence: 2 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Anatomy & Physiology Chemistry |
EISSN | 1742-4658 |
EndPage | 960 |
ExternalDocumentID | oai_gup_ub_gu_se_294294 oai_HAL_hal_02862262v1 10_1111_febs_15372 32446294 FEBS15372 |
Genre | article Journal Article |
GrantInformation_xml | – fundername: EU H2020 MSCA funderid: ITN‐675448; RISE‐734749 – fundername: Agence Nationale de la Recherche funderid: 2014‐3914 – fundername: Fondation pour la Recherche Médicale – fundername: Institut National Du Cancer – fundername: Vetenskapsrådet funderid: 2014‐3914 – fundername: EU H2020 MSCA grantid: RISE-734749 – fundername: Vetenskapsrådet grantid: 2014-3914 – fundername: Agence Nationale de la Recherche grantid: 2014-3914 – fundername: EU H2020 MSCA grantid: ITN-675448 |
GroupedDBID | --- -DZ -~X .3N .55 .GA .Y3 05W 0R~ 10A 1OC 24P 29H 31~ 33P 36B 3O- 3SF 4.4 50Y 50Z 51W 51X 52M 52N 52O 52P 52R 52S 52T 52U 52V 52W 52X 53G 5GY 5HH 5LA 5RE 5VS 66C 702 7PT 8-0 8-1 8-3 8-4 8-5 8UM 930 A01 A03 A8Z AAESR AAEVG AAHBH AAHHS AANLZ AAONW AASGY AAXRX AAZKR ABCQN ABCUV ABDBF ABEFU ABEML ABPVW ABQWH ABXGK ACAHQ ACCFJ ACCZN ACFBH ACGFS ACGOF ACIWK ACMXC ACNCT ACPOU ACPRK ACSCC ACXBN ACXQS ADBBV ADBTR ADEOM ADIZJ ADKYN ADMGS ADOZA ADXAS ADZMN AEEZP AEGXH AEIGN AEIMD AENEX AEQDE AEUQT AEUYR AFBPY AFEBI AFFPM AFGKR AFPWT AFRAH AFZJQ AHBTC AIACR AITYG AIURR AIWBW AJBDE ALAGY ALMA_UNASSIGNED_HOLDINGS ALUQN AMBMR AMYDB ATUGU AZBYB AZVAB BAFTC BAWUL BFHJK BHBCM BMXJE BROTX BRXPI BY8 C1A C45 CAG COF CS3 D-6 D-7 D-E D-F DCZOG DIK DPXWK DR2 DRFUL DRMAN DRSTM E3Z EAD EAP EAS EAU EBB EBC EBD EBS EBX EJD EMB EMK EMOBN EST ESTFP ESX EX3 F00 F01 F04 F5P FIJ FUBAC G-S G.N GODZA GX1 H.X HF~ HGLYW HH5 HZI HZ~ IHE IX1 J0M KBYEO LATKE LC2 LC3 LEEKS LH4 LITHE LOXES LP6 LP7 LUTES LW6 LYRES MEWTI MK4 MRFUL MRMAN MRSTM MSFUL MSMAN MSSTM MVM MXFUL MXMAN MXSTM N04 N05 N9A NF~ O66 O9- OBS OIG OK1 OVD P2W P2X P2Z P4B P4D PQQKQ Q.N Q11 QB0 R.K RNS ROL RX1 SUPJJ SV3 TEORI TR2 TUS UB1 V8K W8V W99 WBFHL WBKPD WIH WIJ WIK WIN WOHZO WOQ WOW WQJ WRC WXI WXSBR WYISQ X7M XG1 Y6R ~IA ~KM ~WT NPM AAYXX CITATION 7QL 7QP 7QR 7TK 7TM 7U9 8FD C1K FR3 H94 M7N P64 RC3 7X8 1XC VOOES ADTPV AOWAS F1U |
ID | FETCH-LOGICAL-c4652-e4636220a43f384dc14d3a7903f39f66dc84d344ccb3f6bfb69409de4ae0ae323 |
IEDL.DBID | DR2 |
ISSN | 1742-464X |
IngestDate | Sat Aug 24 00:02:20 EDT 2024 Fri Sep 06 13:09:26 EDT 2024 Fri Aug 16 22:57:51 EDT 2024 Fri Aug 30 23:19:42 EDT 2024 Fri Aug 23 03:14:55 EDT 2024 Sat Sep 28 08:30:30 EDT 2024 Sat Aug 24 01:03:17 EDT 2024 |
IsDoiOpenAccess | true |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 3 |
Keywords | inhibitors unfolded protein response glioblastoma endoplasmic reticulum IRE1 Inhibitors Endoplasmic Reticulum Unfolded Protein Response |
Language | English |
License | Attribution 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. Attribution: http://creativecommons.org/licenses/by |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c4652-e4636220a43f384dc14d3a7903f39f66dc84d344ccb3f6bfb69409de4ae0ae323 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ORCID | 0000-0002-0105-8066 0000-0001-9807-5278 0000-0001-5855-4522 0000-0002-8318-7784 0000-0002-8610-8375 0000-0003-0873-9873 0000-0002-2996-5733 0000-0001-5654-3109 |
OpenAccessLink | https://proxy.k.utb.cz/login?url=https://onlinelibrary.wiley.com/doi/abs/10.1111%2Ffebs.15372 |
PMID | 32446294 |
PQID | 2484223963 |
PQPubID | 28478 |
PageCount | 16 |
ParticipantIDs | swepub_primary_oai_gup_ub_gu_se_294294 hal_primary_oai_HAL_hal_02862262v1 proquest_miscellaneous_2406307281 proquest_journals_2484223963 crossref_primary_10_1111_febs_15372 pubmed_primary_32446294 wiley_primary_10_1111_febs_15372_FEBS15372 |
PublicationCentury | 2000 |
PublicationDate | February 2021 |
PublicationDateYYYYMMDD | 2021-02-01 |
PublicationDate_xml | – month: 02 year: 2021 text: February 2021 |
PublicationDecade | 2020 |
PublicationPlace | England |
PublicationPlace_xml | – name: England – name: Oxford |
PublicationTitle | The FEBS journal |
PublicationTitleAlternate | FEBS J |
PublicationYear | 2021 |
Publisher | Blackwell Publishing Ltd Wiley |
Publisher_xml | – name: Blackwell Publishing Ltd – name: Wiley |
References | 2004; 200 2015; 6 2010; 38 2010; 15 2019; 6 2018; 128 2017; 22 2004; 47 2004; 25 2015; 55 1983; 5 2017; 23 2006; 7 2011; 30 2008; 10 2000; 2 1948; 238 2015; 7 2019; 287 2012; 109 2019; 286 2016; 11 1989; 74 2018; 9 2001; 60 2014; 5 2013; 12 2006; 49 2019 2018 1988; 110 2008; 456 2011; 25 2018; 10 2014; 6 2012; 8 2018; 36 2006; 443 2019; 176 e_1_2_9_30_1 e_1_2_9_31_1 e_1_2_9_11_1 e_1_2_9_34_1 e_1_2_9_10_1 e_1_2_9_35_1 e_1_2_9_13_1 e_1_2_9_32_1 e_1_2_9_12_1 e_1_2_9_33_1 e_1_2_9_15_1 e_1_2_9_38_1 e_1_2_9_14_1 e_1_2_9_39_1 e_1_2_9_17_1 e_1_2_9_36_1 e_1_2_9_16_1 e_1_2_9_37_1 e_1_2_9_19_1 e_1_2_9_18_1 e_1_2_9_41_1 e_1_2_9_20_1 e_1_2_9_40_1 e_1_2_9_22_1 e_1_2_9_21_1 e_1_2_9_24_1 e_1_2_9_23_1 e_1_2_9_8_1 e_1_2_9_7_1 e_1_2_9_6_1 e_1_2_9_5_1 e_1_2_9_4_1 e_1_2_9_3_1 e_1_2_9_2_1 e_1_2_9_9_1 e_1_2_9_26_1 e_1_2_9_25_1 Carlesso A (e_1_2_9_27_1) 2019; 6 e_1_2_9_28_1 e_1_2_9_29_1 |
References_xml | – volume: 109 start-page: E869 year: 2012 end-page: E878 article-title: The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1‐binding small molecule publication-title: Proc Natl Acad Sci USA – volume: 6 start-page: 1 year: 2019 end-page: 14 article-title: Effect of kinase inhibiting RNase attenuator (KIRA) compounds on the formation of face‐to‐face dimers of inositol‐requiring enzyme 1: insights from computational modeling publication-title: Int J Mol Sci – volume: 5 start-page: 4881 year: 2014 end-page: 4894 article-title: Selective inhibition of unfolded protein response induces apoptosis in pancreatic cancer cells publication-title: Oncotarget – volume: 12 start-page: 703 year: 2013 end-page: 719 article-title: Targeting the unfolded protein response in disease publication-title: Nat Rev Drug Discov – volume: 200 start-page: 35 year: 2004 end-page: 46 article-title: A new family of potent AB cytotoxins produced by Shiga toxigenic publication-title: J Exp Med – volume: 128 start-page: 1283 year: 2018 end-page: 1299 article-title: Pharmacological targeting of MYC‐regulated IRE1/XBP1 pathway suppresses MYC‐driven breast cancer publication-title: J Clin Invest – volume: 286 start-page: 241 year: 2019 end-page: 278 article-title: Endoplasmic reticulum stress signalling – from basic mechanisms to clinical applications publication-title: FEBS J – volume: 15 start-page: 406 year: 2010 end-page: 417 article-title: AlphaScreen‐based characterization of the bifunctional kinase/RNase IRE1α: a novel and atypical drug target publication-title: J Biomol Screen – volume: 238 start-page: 787 year: 1948 end-page: 793 article-title: Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4‐aminopteroyl‐glutamic acid (aminopterin) publication-title: N Engl J Med – volume: 38 start-page: 291 year: 2010 end-page: 304 article-title: Flavonol activation defines an unanticipated ligand‐binding site in the kinase‐RNase domain of IRE1 publication-title: Mol Cell – volume: 9 start-page: 3267 year: 2018 article-title: Inhibition of IRE1 RNase activity modulates the tumor cell secretome and enhances response to chemotherapy publication-title: Nat Commun – volume: 110 start-page: 1657 year: 1988 end-page: 1666 article-title: The OPLS force field for proteins. Energy minimizations for crystals of cyclic peptides and crambin publication-title: J Am Chem Soc – volume: 74 start-page: 19 year: 1989 end-page: 25 article-title: Fludarabine: a new agent with major activity against chronic lymphocytic leukemia publication-title: Blood – volume: 6 start-page: 68 year: 2014 end-page: 72 article-title: Unfolded protein response in cancer: IRE1α inhibition by selective kinase ligands does not impair tumor cell viability publication-title: ACS Med Chem Lett – volume: 60 start-page: 729 year: 2001 end-page: 735 article-title: Anti‐inflammatory mechanisms of methotrexate in rheumatoid arthritis publication-title: Ann Rheum Dis – volume: 287 start-page: 27 year: 2019 end-page: 42 article-title: A guide to assessing endoplasmic reticulum homeostasis and stress in mammalian systems publication-title: FEBS J – volume: 5 start-page: S108 year: 1983 end-page: S126 article-title: Cefoperazone: a review of its antimicrobial spectrum, β‐lactamase stability, enzyme inhibition, and other in vitro characteristics publication-title: Rev Infect Dis – volume: 25 start-page: 3115 year: 2011 end-page: 3129 article-title: Peptides derived from the bifunctional kinase/RNase enzyme IRE1α modulate IRE1α activity and protect cells from endoplasmic reticulum stress publication-title: FASEB J – year: 2018 – volume: 11 start-page: 2195 year: 2016 end-page: 2205 article-title: Structural and functional analysis of the allosteric inhibition of IRE1α with ATP‐competitive ligands publication-title: ACS Chem Biol – volume: 23 start-page: 7360 year: 2017 end-page: 7374 article-title: CD90 expression controls migration and predicts dasatinib response in glioblastoma publication-title: Clin Cancer Res – volume: 6 start-page: 40692 year: 2015 end-page: 40703 article-title: A novel chemical, STF‐083010, reverses tamoxifen‐related drug resistance in breast cancer by inhibiting IRE1/XBP1 publication-title: Oncotarget – volume: 7 start-page: 11 year: 2006 article-title: SuperMimic–fitting peptide mimetics into protein structures publication-title: BMC Bioinformatics – volume: 47 start-page: 1750 year: 2004 end-page: 1759 article-title: Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening publication-title: J Med Chem – volume: 10 year: 2018 article-title: Dual IRE1 RNase functions dictate glioblastoma development publication-title: EMBO Mol Med – volume: 7 start-page: 788 year: 2015 end-page: 801 article-title: Divergent androgen regulation of unfolded protein response pathways drives prostate cancer publication-title: EMBO Mol Med – volume: 49 start-page: 6177 year: 2006 end-page: 6196 article-title: Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein−ligand complexes publication-title: J Med Chem – volume: 22 start-page: 787 year: 2017 end-page: 800 article-title: Control of the unfolded protein response in health and disease publication-title: SLAS Discov Adv Life Sci R&D – volume: 443 start-page: 548 year: 2006 end-page: 552 article-title: AB subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP publication-title: Nature – volume: 2 start-page: 326 year: 2000 end-page: 332 article-title: Dynamic interaction of BiP and ER stress transducers in the unfolded‐protein response publication-title: Nat Cell Biol – year: 2019 article-title: Development of a novel preclinical glioblastoma mouse model and therapeutic impact of IRE1 inhibition publication-title: bioRxiv – volume: 25 start-page: 1605 year: 2004 end-page: 1612 article-title: UCSF Chimera – a visualization system for exploratory research and analysis publication-title: J Comput Chem – volume: 30 start-page: 894 year: 2011 end-page: 905 article-title: Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response publication-title: EMBO J – volume: 55 start-page: 2324 year: 2015 end-page: 2337 article-title: ZINC 15–ligand discovery for everyone publication-title: J Chem Inf Model – volume: 36 start-page: 795 year: 2018 end-page: 803 article-title: Low‐dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis. Results of a multicenter randomized, double‐blind, placebo‐controlled trial publication-title: Arthritis Rheum – volume: 176 start-page: 43 year: 2019 end-page: 55 article-title: Methotrexate chemotherapy induces persistent tri‐glial dysregulation that underlies chemotherapy‐related cognitive impairment publication-title: Cell – volume: 8 start-page: 982 year: 2012 end-page: 989 article-title: Divergent allosteric control of the IRE1α endoribonuclease using kinase inhibitors publication-title: Nat Chem Biol – volume: 5 start-page: 4202 year: 2014 article-title: Structure and mechanism of action of the hydroxy–aryl–aldehyde class of IRE1 endoribonuclease inhibitors publication-title: Nat Commun – volume: 10 start-page: 1775 year: 2008 end-page: 1786 article-title: Subtilase cytotoxin activates PERK, IRE1 and ATF6 endoplasmic reticulum stress‐signalling pathways publication-title: Cell Microbiol – volume: 456 start-page: 648 year: 2008 end-page: 652 article-title: Incorporation of a non‐human glycan mediates human susceptibility to a bacterial toxin publication-title: Nature – ident: e_1_2_9_6_1 doi: 10.15252/emmm.201404509 – ident: e_1_2_9_28_1 doi: 10.1016/j.molcel.2010.04.001 – ident: e_1_2_9_2_1 doi: 10.1111/febs.14608 – ident: e_1_2_9_3_1 doi: 10.1177/2472555217701685 – ident: e_1_2_9_40_1 doi: 10.1002/jcc.20084 – ident: e_1_2_9_12_1 doi: 10.1038/nchembio.1094 – ident: e_1_2_9_5_1 doi: 10.18632/oncotarget.5827 – ident: e_1_2_9_21_1 doi: 10.1021/ja00214a001 – ident: e_1_2_9_23_1 doi: 10.1136/ard.60.8.729 – ident: e_1_2_9_35_1 doi: 10.1016/j.cell.2018.10.049 – volume: 6 start-page: 1 year: 2019 ident: e_1_2_9_27_1 article-title: Effect of kinase inhibiting RNase attenuator (KIRA) compounds on the formation of face‐to‐face dimers of inositol‐requiring enzyme 1: insights from computational modeling publication-title: Int J Mol Sci contributor: fullname: Carlesso A – ident: e_1_2_9_17_1 doi: 10.1038/emboj.2011.18 – ident: e_1_2_9_9_1 doi: 10.1101/841296 – ident: e_1_2_9_32_1 doi: 10.1038/35014014 – ident: e_1_2_9_18_1 doi: 10.1021/ml500315b – ident: e_1_2_9_25_1 doi: 10.1093/clinids/5.Supplement_1.S108 – ident: e_1_2_9_29_1 doi: 10.1158/1078-0432.CCR-17-1549 – ident: e_1_2_9_8_1 doi: 10.1038/s41467-018-05763-8 – ident: e_1_2_9_31_1 doi: 10.1038/nature05124 – ident: e_1_2_9_11_1 doi: 10.1038/nrd3976 – ident: e_1_2_9_38_1 doi: 10.1084/jem.20040392 – ident: e_1_2_9_14_1 doi: 10.1096/fj.11-182931 – ident: e_1_2_9_37_1 doi: 10.1038/ncomms5202 – ident: e_1_2_9_39_1 doi: 10.1186/1471-2105-7-11 – ident: e_1_2_9_36_1 doi: 10.1073/pnas.1115623109 – ident: e_1_2_9_13_1 doi: 10.1021/acschembio.5b00940 – ident: e_1_2_9_30_1 doi: 10.1111/j.1462-5822.2008.01164.x – ident: e_1_2_9_22_1 doi: 10.1056/NEJM194806032382301 – ident: e_1_2_9_4_1 doi: 10.15252/emmm.201707929 – ident: e_1_2_9_10_1 doi: 10.1172/JCI95873 – ident: e_1_2_9_24_1 doi: 10.1002/art.1780360609 – ident: e_1_2_9_16_1 doi: 10.1021/jm030644s – ident: e_1_2_9_26_1 doi: 10.1182/blood.V74.1.19.bloodjournal74119 – ident: e_1_2_9_34_1 – ident: e_1_2_9_20_1 doi: 10.1021/jm051256o – ident: e_1_2_9_15_1 doi: 10.1177/1087057110363823 – ident: e_1_2_9_41_1 doi: 10.1111/febs.15107 – ident: e_1_2_9_7_1 doi: 10.18632/oncotarget.2051 – ident: e_1_2_9_33_1 doi: 10.1038/nature07428 – ident: e_1_2_9_19_1 doi: 10.1021/acs.jcim.5b00559 |
SSID | ssj0035499 |
Score | 2.4770074 |
Snippet | Inositol‐requiring enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of the unfolded protein response... Inositol-requiring enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of the unfolded protein response... Inositol Requiring Enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of the Unfolded Protein Response... |
SourceID | swepub hal proquest crossref pubmed wiley |
SourceType | Open Access Repository Aggregation Database Index Database Publisher |
StartPage | 945 |
SubjectTerms | Biochemistry & Molecular Biology Biochemistry and Molecular Biology Biokemi och molekylärbiologi Cancer Cefoperazone Cell culture Chemotherapy docking Endoplasmic reticulum Fludarabine Folinic acid glide Glioblastoma Glioblastoma cells Human performance Hypoxia Inhibitors Inositol IRE1 ire1-alpha Kinases Life Sciences Methotrexate Optimization peptides Protein folding Protein-serine/threonine kinase Proteins response selective-inhibition Temozolomide Tumors unfolded protein unfolded protein response |
Title | Peptidomimetic‐based identification of FDA‐approved compounds inhibiting IRE1 activity |
URI | https://onlinelibrary.wiley.com/doi/abs/10.1111%2Ffebs.15372 https://www.ncbi.nlm.nih.gov/pubmed/32446294 https://www.proquest.com/docview/2484223963/abstract/ https://search.proquest.com/docview/2406307281 https://univ-rennes.hal.science/hal-02862262 https://gup.ub.gu.se/publication/294294 |
Volume | 288 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwEB61vcCFRws0pVThoR6QstrYXmcjcVnKrhYEqCpUWiEhy07sdoU2WzWbSnDiJ_Ab-SXMOA9YkJDgFtnjxLFn7Jnkm88AT2KDsb8b8kgmLIuEMGmUam6iRGrUp0z2naRE4Tdv5fRUvJoNZhvwrM2Fqfkhug9uZBl-vSYD16b8xcidNWUP7TWhBZiY9MgjOum4ozgFPnU2JIuEFLOGm5RgPD-bru1Gm-eEhfzT0exYRNcdWL8DTW7Cx7bvNfDkU69amV725Tdax_99uVtwo3FNw1GtS7dhwxbbsDMqMCxffA4PQw8W9V_ht-HaUXtQ3A58OCZkTL5czBeUEfn96zfaGvNwnjdIJD_54dKFkxcjrPU05lcoQHB2OtWpDOfF-dzMCYEdvjwZxyFlW9ChFnfgdDJ-fzSNmiMbokzIAYss8Y8x1teCOz4UeRaLnOuE9IGnTso8w0IuRJYZ7qRxRqYYYOZWaNvXljN-F7aKZWF3IXR94aQbOI5iuIMKzXga68xi2zjN0ySAx-3UqYuamUO1EQ0Nn_LDF8AjnNVOgMi0p6PXisrQs8KuSnYVB7DfTrpqTLhUTAwF-k64QAXwsKvGoaU_Krqwy4pkiLIsYUO8xb1aWbpHoacqJEtFAIe19qx14qy6UFh0VqnSKpTygk-9SvzlbdRk_Pydv9r7F-H7cJ0RFMeDzfdha3VZ2QfoS63MAWwycXzgLecHOskb9w |
link.rule.ids | 230,315,786,790,891,1382,11589,27957,27958,46087,46329,46511,46753 |
linkProvider | Wiley-Blackwell |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwELagHMoFSssjpYB5qAekrDa219kct2VXW9hWqLTSiotlJ3Yboc1WzaYSnPgJ_Mb-ks442cCChAS3yJm87Bl7xvnmG0LeRAZif9fnoYxZGgphkjDR3ISx1KBPqew6iYnCh0dyfCreT3vTBpuDuTA1P0S74YaW4edrNHDckP7Fyp01ZQcMNoYZ-A7Ye89HVMctexTH0KfOh2ShkGLasJMikOfntSvr0e1zREP-6Wq2PKKrLqxfg0b360KrpacuROjJl061MJ3022_Ejv_9eRvkXuOd0kGtTg_ILVtskq1BAZH57CvdpR4v6jfiN8n6_rJW3Bb5_BHBMdl8ls8wKfL6-w9cHTOaZw0YyY8_nTs6ejeAs57J_AoEENGOhZ1KmhfnuckRhE0PjocRxYQLrGvxkJyOhif747Cp2hCmQvZYaJGCjLGuFtzxvsjSSGRcx6gSPHFSZik0ciHS1HAnjTMygRgzs0Lbrrac8UdkrZgX9gmhriucdD3HQQwWUaEZTyKdWrg2SrIkDsjr5dipi5qcQy2DGuw-5bsvIK9gWFsB5NMeDyYK28C5gleV7CoKyM5y1FVjxaVioi_AfYI5KiAv29PQtfhTRRd2XqEMspbFrA-3eFxrS_socFaFZIkIyG6tPisvcVZdKGg6q1RpFUh5wbdeJ_7yNWo03Pvkj7b_RfgFWR-fHE7U5ODow1NylyEyx2PPd8ja4rKyz8C1Wpjn3oBuAEEMH0I |
linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1bb9MwFD4aQwJeuGxcAgPMRXtAStXYrtNIvJS1VQdjmgaTqknIysXeItS0os0keOIn8Bv5JZzjXKAgIcFbZB8njn2OfU7ync8Az4MEY3_bF74KeepLmUR-FIvED1WM-pSqrlWUKPz2UE1O5Otpb7oBL5tcmIofov3gRpbh1msy8EVmfzFya5JlB-01xAX4slSCk04Pj1vyKEGRT5UOyX2p5LQmJyUcz8-2a9vRpXMCQ_7pabY0ouserNuCxjfgQ9P5CnnysVOukk765Tdex_99u5twvfZN2aBSpluwYYot2B4UGJfPPrNd5tCi7jP8Flzda06K24bTI4LGZPNZPqOUyO9fv9HemLE8q6FIbvbZ3LLxcIC1jsf8AgUIz07HOi1ZXpznSU4QbLZ_PAoYpVvQqRa34WQ8er838eszG_xUqh73DRGQcd6NpbCiL7M0kJmIQ1IIEVmlshQLhZRpmgirEpuoCCPMzMjYdGMjuLgDm8W8MPeA2a60yvasQDHcQmXMRRTEqcG2QZRFoQfPmqnTi4qaQzchDQ2fdsPnwVOc1VaA2LQngwNNZehaYVcVvwg82GkmXdc2vNRc9iU6T7hCefCkrcahpV8qcWHmJckQZ1nI-3iLu5WytI9CV1UqHkkPdivtWevEWbnQWHRW6qXRKOUEXziV-Mvb6PHo1Tt3df9fhB_DlaPhWB_sH755ANc4wXIc8HwHNlefSvMQ_apV8siZzw_UgB3x |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Peptidomimetic-based+identification+of+FDA-approved+compounds+inhibiting+IRE1+activity&rft.jtitle=The+FEBS+journal&rft.au=Doultsinos%2C+Dimitrios&rft.au=Carlesso%2C+Antonio&rft.au=Chintha%2C+Chetan&rft.au=Paton%2C+James+C&rft.date=2021-02-01&rft.eissn=1742-4658&rft.volume=288&rft.issue=3&rft.spage=945&rft.epage=960&rft_id=info:doi/10.1111%2Ffebs.15372&rft.externalDBID=NO_FULL_TEXT |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1742-464X&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1742-464X&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1742-464X&client=summon |