Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474
A recent phase 1 trial of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 led to the death of one volunteer and produced mild-to-severe neurological symptoms in four others. Although the cause of the clinical neurotoxicity is unknown, it has been postulated, given the clinical safety pro...
Gespeichert in:
| Veröffentlicht in: | Science (American Association for the Advancement of Science) Jg. 356; H. 6342; S. 1084 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
United States
09.06.2017
|
| Schlagworte: | |
| ISSN: | 1095-9203, 1095-9203 |
| Online-Zugang: | Weitere Angaben |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Abstract | A recent phase 1 trial of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 led to the death of one volunteer and produced mild-to-severe neurological symptoms in four others. Although the cause of the clinical neurotoxicity is unknown, it has been postulated, given the clinical safety profile of other tested FAAH inhibitors, that off-target activities of BIA 10-2474 may have played a role. Here we use activity-based proteomic methods to determine the protein interaction landscape of BIA 10-2474 in human cells and tissues. This analysis revealed that the drug inhibits several lipases that are not targeted by PF04457845, a highly selective and clinically tested FAAH inhibitor. BIA 10-2474, but not PF04457845, produced substantial alterations in lipid networks in human cortical neurons, suggesting that promiscuous lipase inhibitors have the potential to cause metabolic dysregulation in the nervous system. |
|---|---|
| AbstractList | A recent phase 1 trial of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 led to the death of one volunteer and produced mild-to-severe neurological symptoms in four others. Although the cause of the clinical neurotoxicity is unknown, it has been postulated, given the clinical safety profile of other tested FAAH inhibitors, that off-target activities of BIA 10-2474 may have played a role. Here we use activity-based proteomic methods to determine the protein interaction landscape of BIA 10-2474 in human cells and tissues. This analysis revealed that the drug inhibits several lipases that are not targeted by PF04457845, a highly selective and clinically tested FAAH inhibitor. BIA 10-2474, but not PF04457845, produced substantial alterations in lipid networks in human cortical neurons, suggesting that promiscuous lipase inhibitors have the potential to cause metabolic dysregulation in the nervous system.A recent phase 1 trial of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 led to the death of one volunteer and produced mild-to-severe neurological symptoms in four others. Although the cause of the clinical neurotoxicity is unknown, it has been postulated, given the clinical safety profile of other tested FAAH inhibitors, that off-target activities of BIA 10-2474 may have played a role. Here we use activity-based proteomic methods to determine the protein interaction landscape of BIA 10-2474 in human cells and tissues. This analysis revealed that the drug inhibits several lipases that are not targeted by PF04457845, a highly selective and clinically tested FAAH inhibitor. BIA 10-2474, but not PF04457845, produced substantial alterations in lipid networks in human cortical neurons, suggesting that promiscuous lipase inhibitors have the potential to cause metabolic dysregulation in the nervous system. A recent phase 1 trial of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 led to the death of one volunteer and produced mild-to-severe neurological symptoms in four others. Although the cause of the clinical neurotoxicity is unknown, it has been postulated, given the clinical safety profile of other tested FAAH inhibitors, that off-target activities of BIA 10-2474 may have played a role. Here we use activity-based proteomic methods to determine the protein interaction landscape of BIA 10-2474 in human cells and tissues. This analysis revealed that the drug inhibits several lipases that are not targeted by PF04457845, a highly selective and clinically tested FAAH inhibitor. BIA 10-2474, but not PF04457845, produced substantial alterations in lipid networks in human cortical neurons, suggesting that promiscuous lipase inhibitors have the potential to cause metabolic dysregulation in the nervous system. |
| Author | van Esbroeck, Annelot C M van der Stelt, Mario Lin, Zhanmin Hendriks, Giel den Dulk, Hans Florea, Bogdan I Fezza, Filomena Hankemeier, Thomas Soethoudt, Marjolein Kushner, Steven A De Petrocellis, Luciano Allarà, Marco van der Kroeg, Mark van der Wel, Tom Janssen, Antonius P A Di Marzo, Vincenzo Cravatt, Benjamin F Kantae, Vasudev Baak, Ilse L Baggelaar, Marc P de Vrij, Femke M S Cognetta, 3rd, Armand B Overkleeft, Herman S Maccarrone, Mauro De Zeeuw, Chris I Ogasawara, Daisuke Shpak, Guy Deng, Hui Mock, Elliot D |
| Author_xml | – sequence: 1 givenname: Annelot C M orcidid: 0000-0003-0631-2403 surname: van Esbroeck fullname: van Esbroeck, Annelot C M organization: Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, Netherlands – sequence: 2 givenname: Antonius P A orcidid: 0000-0003-4203-261X surname: Janssen fullname: Janssen, Antonius P A organization: Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, Netherlands – sequence: 3 givenname: Armand B orcidid: 0000-0003-0773-0674 surname: Cognetta, 3rd fullname: Cognetta, 3rd, Armand B organization: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA – sequence: 4 givenname: Daisuke orcidid: 0000-0002-2178-4698 surname: Ogasawara fullname: Ogasawara, Daisuke organization: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA – sequence: 5 givenname: Guy orcidid: 0000-0001-7874-1448 surname: Shpak fullname: Shpak, Guy organization: Department of Psychiatry, Erasmus University Medical Centre, 3000 CA, Rotterdam, Netherlands – sequence: 6 givenname: Mark orcidid: 0000-0001-5517-3687 surname: van der Kroeg fullname: van der Kroeg, Mark organization: Department of Psychiatry, Erasmus University Medical Centre, 3000 CA, Rotterdam, Netherlands – sequence: 7 givenname: Vasudev orcidid: 0000-0001-8541-0882 surname: Kantae fullname: Kantae, Vasudev organization: Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, Netherlands – sequence: 8 givenname: Marc P orcidid: 0000-0002-9784-6250 surname: Baggelaar fullname: Baggelaar, Marc P organization: Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, Netherlands – sequence: 9 givenname: Femke M S surname: de Vrij fullname: de Vrij, Femke M S organization: Department of Psychiatry, Erasmus University Medical Centre, 3000 CA, Rotterdam, Netherlands – sequence: 10 givenname: Hui orcidid: 0000-0003-0899-4188 surname: Deng fullname: Deng, Hui organization: Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, Netherlands – sequence: 11 givenname: Marco orcidid: 0000-0002-4305-5760 surname: Allarà fullname: Allarà, Marco organization: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche (CNR), Via Campi Flegrei 34, Comprensorio Olivetti, 80078 Pozzuoli, Italy – sequence: 12 givenname: Filomena orcidid: 0000-0003-2263-2909 surname: Fezza fullname: Fezza, Filomena organization: Department of Experimental Medicine and Surgery, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy – sequence: 13 givenname: Zhanmin orcidid: 0000-0002-8188-6733 surname: Lin fullname: Lin, Zhanmin organization: Department of Neuroscience, Erasmus Medical Centre, 3000 CA, Rotterdam, Netherlands – sequence: 14 givenname: Tom orcidid: 0000-0002-6449-3233 surname: van der Wel fullname: van der Wel, Tom organization: Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, Netherlands – sequence: 15 givenname: Marjolein orcidid: 0000-0001-9220-3742 surname: Soethoudt fullname: Soethoudt, Marjolein organization: Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, Netherlands – sequence: 16 givenname: Elliot D orcidid: 0000-0002-1500-2856 surname: Mock fullname: Mock, Elliot D organization: Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, Netherlands – sequence: 17 givenname: Hans orcidid: 0000-0003-4741-3120 surname: den Dulk fullname: den Dulk, Hans organization: Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, Netherlands – sequence: 18 givenname: Ilse L orcidid: 0000-0003-3492-9283 surname: Baak fullname: Baak, Ilse L organization: Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, Netherlands – sequence: 19 givenname: Bogdan I surname: Florea fullname: Florea, Bogdan I organization: Department of Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, Netherlands – sequence: 20 givenname: Giel orcidid: 0000-0001-9506-5082 surname: Hendriks fullname: Hendriks, Giel organization: Toxys B.V., Robert Boyleweg 4, 2333 CG, Leiden, Netherlands – sequence: 21 givenname: Luciano orcidid: 0000-0002-6131-0470 surname: De Petrocellis fullname: De Petrocellis, Luciano organization: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche (CNR), Via Campi Flegrei 34, Comprensorio Olivetti, 80078 Pozzuoli, Italy – sequence: 22 givenname: Herman S orcidid: 0000-0001-6976-7005 surname: Overkleeft fullname: Overkleeft, Herman S organization: Department of Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, Netherlands – sequence: 23 givenname: Thomas orcidid: 0000-0001-7871-2073 surname: Hankemeier fullname: Hankemeier, Thomas organization: Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, Netherlands – sequence: 24 givenname: Chris I surname: De Zeeuw fullname: De Zeeuw, Chris I organization: Netherlands Institute for Neuroscience, Royal Dutch Academy of Arts and Sciences, 1105 BA, Amsterdam, Netherlands – sequence: 25 givenname: Vincenzo orcidid: 0000-0002-1490-3070 surname: Di Marzo fullname: Di Marzo, Vincenzo organization: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche (CNR), Via Campi Flegrei 34, Comprensorio Olivetti, 80078 Pozzuoli, Italy – sequence: 26 givenname: Mauro orcidid: 0000-0002-3990-2963 surname: Maccarrone fullname: Maccarrone, Mauro organization: Department of Medicine, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy – sequence: 27 givenname: Benjamin F orcidid: 0000-0001-5330-3492 surname: Cravatt fullname: Cravatt, Benjamin F organization: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA – sequence: 28 givenname: Steven A orcidid: 0000-0002-9777-3338 surname: Kushner fullname: Kushner, Steven A email: m.van.der.stelt@chem.leidenuniv.nl, s.kushner@erasmusmc.nl organization: Department of Psychiatry, Erasmus University Medical Centre, 3000 CA, Rotterdam, Netherlands. m.van.der.stelt@chem.leidenuniv.nl s.kushner@erasmusmc.nl – sequence: 29 givenname: Mario orcidid: 0000-0002-1029-5717 surname: van der Stelt fullname: van der Stelt, Mario email: m.van.der.stelt@chem.leidenuniv.nl, s.kushner@erasmusmc.nl organization: Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, Netherlands. m.van.der.stelt@chem.leidenuniv.nl s.kushner@erasmusmc.nl |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28596366$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkD1PwzAQhi1URD9gZkMeWVJsx3acMVSUVqrEAiuRY19ao9QpsVup_76paCWm9-703OnRjdHAtx4QeqRkSimTL8E48AamWtcZz7MbNKIkF0nOSDr4Vw_ROIQfQvo-T-_QkCmRy1TKEfouTHQHF49JpQNYvOvaCM6fs3aN82vcwQF0E3Bb10nU3RriFTrPcNwAnhfFAju_cZWLbYdflwWmJGE84_fotu6X4eGSE_Q1f_ucLZLVx_tyVqwSIziLSSqtZJXUwnKqtMiUlb2s1dzYXhMUE0RzZRlTGXBLaCUMo5kQVNqaSWPZBD3_3e3VfvcQYrl1wUDTaA_tPpQ0J4qnjIi0R58u6L7agi13ndvq7lhef8JOJZxktw |
| CitedBy_id | crossref_primary_10_1186_s12967_018_1678_1 crossref_primary_10_1002_cpt_1145 crossref_primary_10_1080_17460441_2020_1751118 crossref_primary_10_1038_nprot_2017_159 crossref_primary_10_1016_j_cell_2020_01_025 crossref_primary_10_1111_joim_13229 crossref_primary_10_1016_j_bmc_2019_03_020 crossref_primary_10_1002_advs_202305608 crossref_primary_10_1002_cbic_201900674 crossref_primary_10_1002_cbic_202000542 crossref_primary_10_3390_cells14070551 crossref_primary_10_1002_pmic_201700270 crossref_primary_10_33549_physiolres_935371 crossref_primary_10_1016_j_isci_2024_110642 crossref_primary_10_1097_MCG_0000000000001393 crossref_primary_10_2147_DDDT_S462785 crossref_primary_10_1016_j_ejmech_2020_112353 crossref_primary_10_1016_j_vascn_2020_106677 crossref_primary_10_1038_s41386_018_0274_7 crossref_primary_10_1007_s10286_017_0488_5 crossref_primary_10_1016_S2215_0366_18_30427_9 crossref_primary_10_1038_s43586_021_00028_z crossref_primary_10_1111_febs_14744 crossref_primary_10_1016_j_pbb_2021_173192 crossref_primary_10_1002_cbic_201800257 crossref_primary_10_3390_ijms21041423 crossref_primary_10_1002_cbf_3680 crossref_primary_10_1016_j_yrtph_2019_104555 crossref_primary_10_1016_j_yrtph_2019_104556 crossref_primary_10_1080_14756366_2018_1532418 crossref_primary_10_1002_cbic_202200690 crossref_primary_10_1016_j_microc_2020_105445 crossref_primary_10_3390_ph11020055 crossref_primary_10_1016_j_neulet_2021_136064 crossref_primary_10_1038_s41598_018_30553_z crossref_primary_10_1002_ijch_202200115 crossref_primary_10_1002_ijch_202200113 crossref_primary_10_1016_j_phytochem_2022_113282 crossref_primary_10_1021_jacs_4c18083 crossref_primary_10_1002_anie_202311190 crossref_primary_10_1002_cmdc_202000310 crossref_primary_10_1016_j_bmcl_2020_127118 crossref_primary_10_1016_j_plipres_2022_101194 crossref_primary_10_1038_s41586_024_07865_4 crossref_primary_10_1007_s40429_024_00588_6 crossref_primary_10_1016_j_mcn_2023_103842 crossref_primary_10_1016_j_pnpbp_2019_03_017 crossref_primary_10_1186_s13321_018_0297_4 crossref_primary_10_1089_can_2021_0237 crossref_primary_10_1002_jcph_1000 crossref_primary_10_1016_j_bmcl_2020_127463 crossref_primary_10_1007_s40429_020_00342_8 crossref_primary_10_1016_j_lfs_2017_09_033 crossref_primary_10_3390_ijms23126851 crossref_primary_10_1016_j_ejmech_2019_111953 crossref_primary_10_1021_jacs_2c10819 crossref_primary_10_1155_2020_8438272 crossref_primary_10_1016_j_apsb_2019_10_006 crossref_primary_10_1038_s41386_020_00888_1 crossref_primary_10_17269_s41997_020_00333_2 crossref_primary_10_1002_ejoc_202001507 crossref_primary_10_1080_17476348_2018_1507736 crossref_primary_10_1021_acs_chemrev_5c00001 crossref_primary_10_1016_j_pnpbp_2020_110116 crossref_primary_10_1111_acer_14159 crossref_primary_10_1038_npp_2017_204 crossref_primary_10_1080_14789450_2020_1873134 crossref_primary_10_1146_annurev_pharmtox_033123_123610 crossref_primary_10_3390_ijms232415502 crossref_primary_10_3390_biomedicines10081789 crossref_primary_10_1093_toxsci_kfx266 crossref_primary_10_1002_cmdc_202400791 crossref_primary_10_1038_s41596_020_0352_2 crossref_primary_10_1002_cmdc_201800397 crossref_primary_10_1002_cmdc_201800393 crossref_primary_10_3390_ijms22020730 crossref_primary_10_1002_cpt_2290 crossref_primary_10_1016_j_bbalip_2018_08_007 crossref_primary_10_1016_j_vascn_2020_106869 crossref_primary_10_1016_j_euroneuro_2019_12_119 crossref_primary_10_1002_cpt_2498 crossref_primary_10_1016_j_pharmthera_2019_107402 crossref_primary_10_1111_bcp_13550 crossref_primary_10_1016_j_euroneuro_2020_08_005 crossref_primary_10_1038_s41598_018_20895_z crossref_primary_10_3390_ijms22116108 crossref_primary_10_1371_journal_pone_0268590 crossref_primary_10_1016_j_pneurobio_2017_10_007 crossref_primary_10_1002_cbic_202000527 crossref_primary_10_1016_j_mehy_2018_04_010 crossref_primary_10_1016_j_addr_2020_06_028 crossref_primary_10_1016_j_lmot_2023_101872 crossref_primary_10_3390_molecules24050918 crossref_primary_10_1016_j_bmc_2022_116698 crossref_primary_10_1038_s41419_023_05779_z crossref_primary_10_3390_ph16040547 crossref_primary_10_1002_ajoc_201800517 crossref_primary_10_1002_pmic_201900325 crossref_primary_10_1080_17460441_2020_1752178 crossref_primary_10_1002_cbic_202400333 crossref_primary_10_1016_j_brainres_2019_146467 crossref_primary_10_3390_molecules25245994 crossref_primary_10_1016_j_bmc_2019_05_050 crossref_primary_10_1016_j_vascn_2018_07_001 crossref_primary_10_1111_jcpp_70006 crossref_primary_10_1002_cbic_202300473 crossref_primary_10_1016_j_cmet_2021_12_011 crossref_primary_10_1016_j_pbb_2020_173059 crossref_primary_10_1016_j_phrs_2019_02_002 crossref_primary_10_3390_ijms20184503 crossref_primary_10_1002_ange_201710482 crossref_primary_10_1038_s41589_020_0528_7 crossref_primary_10_1038_s41573_024_00942_3 crossref_primary_10_1016_j_coph_2020_08_014 crossref_primary_10_1038_nrd_2018_115 crossref_primary_10_1146_annurev_pharmtox_030220_112741 crossref_primary_10_1111_bph_14973 crossref_primary_10_3390_antibiotics11050673 crossref_primary_10_1016_j_tips_2024_09_003 crossref_primary_10_1002_cbic_202200166 crossref_primary_10_1016_j_ejmech_2018_10_021 crossref_primary_10_1515_hsz_2019_0262 crossref_primary_10_1177_0141076818812783 crossref_primary_10_1136_bmj_q1600 crossref_primary_10_3390_neurolint16040057 crossref_primary_10_1002_ange_202311190 crossref_primary_10_1007_s40263_019_00627_1 crossref_primary_10_1002_cbic_202000253 crossref_primary_10_1038_nchembio_2445 crossref_primary_10_1016_j_cell_2022_03_040 crossref_primary_10_1002_cmdc_202200174 crossref_primary_10_35430_nab_2021_e14 crossref_primary_10_1002_cmdc_202100120 crossref_primary_10_1186_s12967_018_1710_5 crossref_primary_10_1016_j_nbd_2019_104624 crossref_primary_10_1186_s12910_019_0352_3 crossref_primary_10_3390_ijms242417379 crossref_primary_10_1002_cmdc_202000153 crossref_primary_10_1021_jacs_7b11281 crossref_primary_10_1016_j_cbpa_2019_10_003 crossref_primary_10_1016_j_drudis_2021_08_010 crossref_primary_10_1093_bbb_zbae094 crossref_primary_10_1039_D1SC01359A crossref_primary_10_1097_WCO_0000000000000688 crossref_primary_10_1002_cbic_202000042 crossref_primary_10_2147_CCID_S286411 crossref_primary_10_1007_s43440_021_00246_y crossref_primary_10_3390_ijms19030833 crossref_primary_10_1038_s41573_022_00409_3 crossref_primary_10_1002_cjoc_202000353 crossref_primary_10_3390_ph14090936 crossref_primary_10_3389_fimmu_2017_01487 crossref_primary_10_1093_brain_awad098 crossref_primary_10_3390_molecules24244626 crossref_primary_10_1002_pmic_201900372 crossref_primary_10_1016_j_bioorg_2022_106031 crossref_primary_10_3389_fnmol_2019_00286 crossref_primary_10_1097_FJC_0000000000001560 crossref_primary_10_1080_10408444_2020_1867821 crossref_primary_10_1016_j_mcpro_2025_100961 crossref_primary_10_1002_ajoc_202100036 crossref_primary_10_1016_j_ejmech_2020_112151 crossref_primary_10_1007_s11055_021_01148_5 crossref_primary_10_1016_j_jad_2018_10_117 crossref_primary_10_1002_anie_201710482 crossref_primary_10_1016_j_yrtph_2019_104540 crossref_primary_10_1016_j_neubiorev_2021_09_002 crossref_primary_10_1016_j_yrtph_2019_104541 crossref_primary_10_1002_ijch_202300016 crossref_primary_10_1016_j_yrtph_2019_104543 crossref_primary_10_1016_j_lfs_2018_04_054 crossref_primary_10_1080_14756366_2021_1875459 crossref_primary_10_1016_j_vascn_2019_106593 crossref_primary_10_1097_j_pain_0000000000001540 crossref_primary_10_1007_s12640_021_00424_z crossref_primary_10_1002_jcph_995 crossref_primary_10_1007_s40263_019_00664_w crossref_primary_10_1080_17425255_2019_1652596 crossref_primary_10_3390_cancers13225701 crossref_primary_10_1016_j_biopsych_2021_07_019 crossref_primary_10_1002_slct_201903375 crossref_primary_10_1016_j_cclet_2022_04_013 crossref_primary_10_1513_AnnalsATS_201908_581PS crossref_primary_10_1007_s00482_018_0299_1 crossref_primary_10_1111_exd_14145 crossref_primary_10_1002_cbic_201900771 crossref_primary_10_1038_s41587_025_02737_2 crossref_primary_10_1038_s41573_020_0063_y crossref_primary_10_1016_j_chemosphere_2022_134359 crossref_primary_10_1080_10426507_2025_2467438 crossref_primary_10_1016_j_coisb_2018_05_002 crossref_primary_10_1016_j_clinthera_2020_03_021 crossref_primary_10_1021_acs_analchem_5c02409 crossref_primary_10_1146_annurev_pharmtox_052120_013205 crossref_primary_10_1007_s12325_023_02492_3 crossref_primary_10_1016_j_comtox_2023_100273 |
| ContentType | Journal Article |
| Copyright | Copyright © 2017, American Association for the Advancement of Science. |
| Copyright_xml | – notice: Copyright © 2017, American Association for the Advancement of Science. |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1126/science.aaf7497 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Sciences (General) Biology |
| EISSN | 1095-9203 |
| ExternalDocumentID | 28596366 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NIDA NIH HHS grantid: R01 DA033760 |
| GroupedDBID | --- --Z -DZ -ET -~X .-4 ..I .55 .DC 08G 0R~ 0WA 123 18M 2FS 2KS 2WC 2XV 34G 36B 39C 3R3 53G 5RE 66. 6OB 6TJ 7X2 7~K 85S 8F7 AABCJ AACGO AADHG AAIKC AAMNW AANCE AAWTO ABBHK ABCQX ABDBF ABDEX ABDQB ABEFU ABIVO ABJNI ABOCM ABPLY ABPPZ ABQIJ ABTLG ABWJO ABXSQ ABZEH ACBEA ACBEC ACGFO ACGFS ACGOD ACHIC ACIWK ACMJI ACNCT ACPRK ACQOY ACUHS ADDRP ADMHC ADQXQ ADUKH ADXHL AEGBM AENEX AETEA AEUPB AEXZC AFBNE AFFDN AFFNX AFHKK AFQFN AFRAH AGNAY AGSOS AHMBA AIDAL AIDUJ AJGZS ALMA_UNASSIGNED_HOLDINGS AQVQM ASPBG ATCPS AVWKF BKF BLC C45 C51 CGR CS3 CUY CVF DB2 DCCCD DU5 EBS ECM EIF EJD EMOBN F5P FA8 FEDTE HZ~ IAO IEA IGS IH2 IHR INH INR IOF IOV IPO IPSME IPY ISE JAAYA JBMMH JCF JENOY JHFFW JKQEH JLS JLXEF JPM JSG JST K-O KCC L7B LSO LU7 M0P MQT MVM N9A NEJ NHB NPM O9- OCB OFXIZ OGEVE OMK OVD P-O P2P PQQKQ PZZ QS- RHI RXW SA0 SC5 SJN TAE TEORI TN5 TWZ UBW UCV UHB UKR UMD UNMZH UQL USG VVN WH7 WI4 X7M XJF XZL Y6R YK4 YKV YNT YOJ YR2 YR5 YRY YSQ YV5 YWH YYP YYQ YZZ ZCA ZE2 ~02 ~G0 ~KM ~ZZ 7X8 |
| ID | FETCH-LOGICAL-c542t-36d62b6a5d418a578d6000da4cd636e8250a48d2287e4d01b5c2175516df26cd2 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 255 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000402871700056&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1095-9203 |
| IngestDate | Sun Nov 09 13:50:13 EST 2025 Sun Nov 23 04:09:13 EST 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 6342 |
| Language | English |
| License | Copyright © 2017, American Association for the Advancement of Science. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c542t-36d62b6a5d418a578d6000da4cd636e8250a48d2287e4d01b5c2175516df26cd2 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0001-7874-1448 0000-0002-3990-2963 0000-0003-0899-4188 0000-0002-6449-3233 0000-0001-9220-3742 0000-0001-9506-5082 0000-0002-9777-3338 0000-0002-1029-5717 0000-0002-1490-3070 0000-0003-3492-9283 0000-0002-2178-4698 0000-0003-2263-2909 0000-0002-9784-6250 0000-0003-4203-261X 0000-0002-6131-0470 0000-0001-5330-3492 0000-0003-0773-0674 0000-0002-8188-6733 0000-0001-5517-3687 0000-0001-7871-2073 0000-0002-4305-5760 0000-0002-1500-2856 0000-0001-6976-7005 0000-0003-0631-2403 0000-0001-8541-0882 0000-0003-4741-3120 |
| OpenAccessLink | https://hdl.handle.net/1887/69129 |
| PMID | 28596366 |
| PQID | 1908432053 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_1908432053 pubmed_primary_28596366 |
| PublicationCentury | 2000 |
| PublicationDate | 2017-06-09 20170609 |
| PublicationDateYYYYMMDD | 2017-06-09 |
| PublicationDate_xml | – month: 06 year: 2017 text: 2017-06-09 day: 09 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Science (American Association for the Advancement of Science) |
| PublicationTitleAlternate | Science |
| PublicationYear | 2017 |
| References | 28853735 - Nat Chem Biol. 2017 Jul 18;13(8):817 |
| References_xml | – reference: 28853735 - Nat Chem Biol. 2017 Jul 18;13(8):817 |
| SSID | ssj0009593 |
| Score | 2.6363158 |
| Snippet | A recent phase 1 trial of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 led to the death of one volunteer and produced mild-to-severe... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 1084 |
| SubjectTerms | Amidohydrolases - antagonists & inhibitors Analgesics - adverse effects Analgesics - chemistry Analgesics - metabolism Analgesics - pharmacology Anti-Anxiety Agents - adverse effects Anti-Anxiety Agents - chemistry Anti-Anxiety Agents - metabolism Anti-Anxiety Agents - pharmacology Cell Line, Tumor Clinical Trials, Phase I as Topic Cross Reactions Cyclic N-Oxides - adverse effects Cyclic N-Oxides - chemistry Cyclic N-Oxides - metabolism Cyclic N-Oxides - pharmacology Humans Neurons - drug effects Neurons - metabolism Protein Interaction Maps Pyridazines - pharmacology Pyridazines - therapeutic use Pyridines - adverse effects Pyridines - chemistry Pyridines - metabolism Pyridines - pharmacology Urea - analogs & derivatives Urea - pharmacology Urea - therapeutic use |
| Title | Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474 |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/28596366 https://www.proquest.com/docview/1908432053 |
| Volume | 356 |
| WOSCitedRecordID | wos000402871700056&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8QwEA7qKnhR1-f6IoIHPUS7SZqmJ6nisoIue1DYk0vaJNhLu25XwX_vpM2iCILgpYfSQJjOzDeTx_chdAoIS7OUSwJ5wBJuQ0qUSBlJBWAts9pQWV8Uvo8GAzkaxUO_4Fb5Y5XznFgnal1mbo38EoBLckbBZ64mr8SpRrndVS-hsYhaDEoZF5jRSP4k3e0GTo-QBsxT-3y7NHOhlI14HP1eX9Y401v_7ww30JqvMHHSuEQbLZhiE600mpMfm6jto7nCZ55y-nwLPSdZoyJBHKppXLM35AVuFL0B3bBjegJPxaW1pDk9Pv_IvcNQRuJekvRxXrzkKWSJKb6-SzBkX8ojvo2eerePN33ilRdIFnI6I0xoQVOhQs27UkFQa6iLAq14pgUTBrrKQHGpKbRbhuugm4YZtDZuz01bKjJNd9BSURZmD-EYKiCuTcjABTgTsWQ8ZpwpGxpuhGIddDK35hg8221XqMKUb9X4y54dtNv8kvGkoeAYO9o9mInY_8PoA7RKHRa7pZP4ELUsWMscoeXsfZZX0-PaZeA5GD58At0AyZ4 |
| linkProvider | ProQuest |
| 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=Activity-based+protein+profiling+reveals+off-target+proteins+of+the+FAAH+inhibitor+BIA+10-2474&rft.jtitle=Science+%28American+Association+for+the+Advancement+of+Science%29&rft.au=van+Esbroeck%2C+Annelot+C+M&rft.au=Janssen%2C+Antonius+P+A&rft.au=Cognetta%2C+Armand+B&rft.au=Ogasawara%2C+Daisuke&rft.date=2017-06-09&rft.issn=1095-9203&rft.eissn=1095-9203&rft.volume=356&rft.issue=6342&rft.spage=1084&rft_id=info:doi/10.1126%2Fscience.aaf7497&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1095-9203&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1095-9203&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1095-9203&client=summon |