PMC:7600245 / 65551-66788
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7600245","sourcedb":"PMC","sourceid":"7600245","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7600245","text":"4.14. BLD-2660\nIt an orally bioavailable, small molecule, reversible covalent inhibitor of calpains, non-lysosomal cysteine proteases, with anti-fibrotic activity. BLD-2660 exhibited potent and selective inhibition of calpains 1,2, and 9 and thus was found to be efficacious in multiple animal fibrosis models of skin, liver, and lung. It exhibited high selectivity against related cysteine proteases. Earlier, several calpain inhibitors were found to reduce the viral replication of SARS-CoV-1 [232,233]. The antiviral activity by calpain inhibition was also verified using siRNA to selectively silence expression of the calpain 2 isoform in SARS-CoV infected cells [232,233]. Undisclosed inhibitors by the developing company were found to reduce SARS-CoV-2 replication in Vero cell-based assays. Furthermore, in preclinical animal models of lung injury and fibrosis, BLD-2660 was shown to reduce the expression/production of IL-6 in injured lungs and to reduce fibrosis [234]. Owing to the antiviral and anti-inflammatory activities of BLD-2660, it has been advanced to a phase 2, randomized, double-blind, placebo-controlled study to evaluate its safety and antiviral activity in COVID-19 hospitalized subjects (NCT04334460; n = 120).","divisions":[{"label":"title","span":{"begin":0,"end":14}}],"tracks":[{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T286","span":{"begin":105,"end":114},"obj":"Body_part"},{"id":"T287","span":{"begin":115,"end":123},"obj":"Body_part"},{"id":"T288","span":{"begin":313,"end":317},"obj":"Body_part"},{"id":"T289","span":{"begin":319,"end":324},"obj":"Body_part"},{"id":"T290","span":{"begin":330,"end":334},"obj":"Body_part"},{"id":"T291","span":{"begin":382,"end":390},"obj":"Body_part"},{"id":"T292","span":{"begin":661,"end":666},"obj":"Body_part"},{"id":"T293","span":{"begin":779,"end":783},"obj":"Body_part"},{"id":"T294","span":{"begin":843,"end":847},"obj":"Body_part"},{"id":"T295","span":{"begin":943,"end":948},"obj":"Body_part"}],"attributes":[{"id":"A286","pred":"fma_id","subj":"T286","obj":"http://purl.org/sig/ont/fma/fma63836"},{"id":"A287","pred":"fma_id","subj":"T287","obj":"http://purl.org/sig/ont/fma/fma82751"},{"id":"A288","pred":"fma_id","subj":"T288","obj":"http://purl.org/sig/ont/fma/fma7163"},{"id":"A289","pred":"fma_id","subj":"T289","obj":"http://purl.org/sig/ont/fma/fma7197"},{"id":"A290","pred":"fma_id","subj":"T290","obj":"http://purl.org/sig/ont/fma/fma7195"},{"id":"A291","pred":"fma_id","subj":"T291","obj":"http://purl.org/sig/ont/fma/fma82751"},{"id":"A292","pred":"fma_id","subj":"T292","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A293","pred":"fma_id","subj":"T293","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A294","pred":"fma_id","subj":"T294","obj":"http://purl.org/sig/ont/fma/fma7195"},{"id":"A295","pred":"fma_id","subj":"T295","obj":"http://purl.org/sig/ont/fma/fma68877"},{"subj":"T286","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T287","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T288","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T289","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T290","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T291","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T292","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T293","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T294","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T295","pred":"source","obj":"LitCovid-PD-FMA-UBERON"}]},{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T30","span":{"begin":313,"end":317},"obj":"Body_part"},{"id":"T31","span":{"begin":319,"end":324},"obj":"Body_part"},{"id":"T32","span":{"begin":330,"end":334},"obj":"Body_part"},{"id":"T33","span":{"begin":843,"end":847},"obj":"Body_part"}],"attributes":[{"id":"A30","pred":"uberon_id","subj":"T30","obj":"http://purl.obolibrary.org/obo/UBERON_0000014"},{"id":"A31","pred":"uberon_id","subj":"T31","obj":"http://purl.obolibrary.org/obo/UBERON_0002107"},{"id":"A32","pred":"uberon_id","subj":"T32","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A33","pred":"uberon_id","subj":"T33","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"subj":"T30","pred":"source","obj":"LitCovid-PD-UBERON"},{"subj":"T31","pred":"source","obj":"LitCovid-PD-UBERON"},{"subj":"T32","pred":"source","obj":"LitCovid-PD-UBERON"},{"subj":"T33","pred":"source","obj":"LitCovid-PD-UBERON"}]},{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T309","span":{"begin":484,"end":492},"obj":"Disease"},{"id":"T310","span":{"begin":643,"end":651},"obj":"Disease"},{"id":"T311","span":{"begin":748,"end":756},"obj":"Disease"},{"id":"T312","span":{"begin":848,"end":854},"obj":"Disease"},{"id":"T313","span":{"begin":1183,"end":1191},"obj":"Disease"}],"attributes":[{"id":"A309","pred":"mondo_id","subj":"T309","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A310","pred":"mondo_id","subj":"T310","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A311","pred":"mondo_id","subj":"T311","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A312","pred":"mondo_id","subj":"T312","obj":"http://purl.obolibrary.org/obo/MONDO_0021178"},{"id":"A313","pred":"mondo_id","subj":"T313","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"subj":"T309","pred":"source","obj":"LitCovid-PD-MONDO"},{"subj":"T310","pred":"source","obj":"LitCovid-PD-MONDO"},{"subj":"T311","pred":"source","obj":"LitCovid-PD-MONDO"},{"subj":"T312","pred":"source","obj":"LitCovid-PD-MONDO"},{"subj":"T313","pred":"source","obj":"LitCovid-PD-MONDO"}]},{"project":"LitCovid-PD-CLO","denotations":[{"id":"T662","span":{"begin":105,"end":114},"obj":"http://purl.obolibrary.org/obo/GO_0005764"},{"id":"T663","span":{"begin":154,"end":162},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T664","span":{"begin":287,"end":293},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_33208"},{"id":"T665","span":{"begin":313,"end":317},"obj":"http://purl.obolibrary.org/obo/UBERON_0000014"},{"id":"T666","span":{"begin":313,"end":317},"obj":"http://purl.obolibrary.org/obo/UBERON_0001003"},{"id":"T667","span":{"begin":313,"end":317},"obj":"http://purl.obolibrary.org/obo/UBERON_0002097"},{"id":"T668","span":{"begin":313,"end":317},"obj":"http://purl.obolibrary.org/obo/UBERON_0002199"},{"id":"T669","span":{"begin":313,"end":317},"obj":"http://www.ebi.ac.uk/efo/EFO_0000962"},{"id":"T670","span":{"begin":319,"end":324},"obj":"http://purl.obolibrary.org/obo/UBERON_0002107"},{"id":"T671","span":{"begin":319,"end":324},"obj":"http://www.ebi.ac.uk/efo/EFO_0000887"},{"id":"T672","span":{"begin":330,"end":334},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T673","span":{"begin":330,"end":334},"obj":"http://www.ebi.ac.uk/efo/EFO_0000934"},{"id":"T674","span":{"begin":520,"end":528},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T675","span":{"begin":661,"end":666},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T676","span":{"begin":774,"end":783},"obj":"http://purl.obolibrary.org/obo/CLO_0009524"},{"id":"T677","span":{"begin":826,"end":832},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_33208"},{"id":"T678","span":{"begin":843,"end":847},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T679","span":{"begin":843,"end":847},"obj":"http://www.ebi.ac.uk/efo/EFO_0000934"},{"id":"T680","span":{"begin":943,"end":948},"obj":"http://www.ebi.ac.uk/efo/EFO_0000934"},{"id":"T681","span":{"begin":1024,"end":1034},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T682","span":{"begin":1051,"end":1054},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T683","span":{"begin":1072,"end":1073},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T684","span":{"begin":1171,"end":1179},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"}],"attributes":[{"subj":"T662","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T663","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T664","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T665","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T666","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T667","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T668","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T669","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T670","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T671","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T672","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T673","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T674","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T675","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T676","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T677","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T678","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T679","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T680","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T681","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T682","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T683","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T684","pred":"source","obj":"LitCovid-PD-CLO"}]},{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T9195","span":{"begin":48,"end":56},"obj":"Chemical"},{"id":"T12773","span":{"begin":78,"end":87},"obj":"Chemical"},{"id":"T3099","span":{"begin":115,"end":123},"obj":"Chemical"},{"id":"T38887","span":{"begin":382,"end":390},"obj":"Chemical"},{"id":"T92042","span":{"begin":419,"end":437},"obj":"Chemical"},{"id":"T53518","span":{"begin":427,"end":437},"obj":"Chemical"},{"id":"T70302","span":{"begin":510,"end":519},"obj":"Chemical"},{"id":"T46598","span":{"begin":690,"end":700},"obj":"Chemical"},{"id":"T12103","span":{"begin":927,"end":929},"obj":"Chemical"},{"id":"T3501","span":{"begin":992,"end":1001},"obj":"Chemical"},{"id":"T97654","span":{"begin":1161,"end":1170},"obj":"Chemical"}],"attributes":[{"id":"A54235","pred":"chebi_id","subj":"T9195","obj":"http://purl.obolibrary.org/obo/CHEBI_25367"},{"id":"A88777","pred":"chebi_id","subj":"T12773","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A20608","pred":"chebi_id","subj":"T3099","obj":"http://purl.obolibrary.org/obo/CHEBI_15356"},{"id":"A69390","pred":"chebi_id","subj":"T38887","obj":"http://purl.obolibrary.org/obo/CHEBI_15356"},{"id":"A49275","pred":"chebi_id","subj":"T92042","obj":"http://purl.obolibrary.org/obo/CHEBI_82824"},{"id":"A95934","pred":"chebi_id","subj":"T53518","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A85106","pred":"chebi_id","subj":"T70302","obj":"http://purl.obolibrary.org/obo/CHEBI_22587"},{"id":"A70346","pred":"chebi_id","subj":"T46598","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A78498","pred":"chebi_id","subj":"T12103","obj":"http://purl.obolibrary.org/obo/CHEBI_63895"},{"id":"A61730","pred":"chebi_id","subj":"T12103","obj":"http://purl.obolibrary.org/obo/CHEBI_74072"},{"id":"A89783","pred":"chebi_id","subj":"T3501","obj":"http://purl.obolibrary.org/obo/CHEBI_22587"},{"id":"A99202","pred":"chebi_id","subj":"T97654","obj":"http://purl.obolibrary.org/obo/CHEBI_22587"},{"subj":"T9195","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T12773","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T3099","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T38887","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T92042","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T53518","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T70302","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T46598","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T12103","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T3501","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T97654","pred":"source","obj":"LitCovid-PD-CHEBI"}]},{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T133","span":{"begin":463,"end":480},"obj":"http://purl.obolibrary.org/obo/GO_0019079"},{"id":"T134","span":{"begin":463,"end":480},"obj":"http://purl.obolibrary.org/obo/GO_0019058"}],"attributes":[{"subj":"T133","pred":"source","obj":"LitCovid-PD-GO-BP"},{"subj":"T134","pred":"source","obj":"LitCovid-PD-GO-BP"}]},{"project":"LitCovid-sentences","denotations":[{"id":"T506","span":{"begin":0,"end":5},"obj":"Sentence"},{"id":"T507","span":{"begin":6,"end":14},"obj":"Sentence"},{"id":"T508","span":{"begin":15,"end":163},"obj":"Sentence"},{"id":"T509","span":{"begin":164,"end":335},"obj":"Sentence"},{"id":"T510","span":{"begin":336,"end":401},"obj":"Sentence"},{"id":"T511","span":{"begin":402,"end":505},"obj":"Sentence"},{"id":"T512","span":{"begin":506,"end":677},"obj":"Sentence"},{"id":"T513","span":{"begin":678,"end":797},"obj":"Sentence"},{"id":"T514","span":{"begin":798,"end":978},"obj":"Sentence"},{"id":"T515","span":{"begin":979,"end":1237},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T506","pred":"source","obj":"LitCovid-sentences"},{"subj":"T507","pred":"source","obj":"LitCovid-sentences"},{"subj":"T508","pred":"source","obj":"LitCovid-sentences"},{"subj":"T509","pred":"source","obj":"LitCovid-sentences"},{"subj":"T510","pred":"source","obj":"LitCovid-sentences"},{"subj":"T511","pred":"source","obj":"LitCovid-sentences"},{"subj":"T512","pred":"source","obj":"LitCovid-sentences"},{"subj":"T513","pred":"source","obj":"LitCovid-sentences"},{"subj":"T514","pred":"source","obj":"LitCovid-sentences"},{"subj":"T515","pred":"source","obj":"LitCovid-sentences"}]},{"project":"LitCovid-PubTator","denotations":[{"id":"2058","span":{"begin":218,"end":237},"obj":"Gene"},{"id":"2059","span":{"begin":622,"end":631},"obj":"Gene"},{"id":"2060","span":{"begin":927,"end":931},"obj":"Gene"},{"id":"2061","span":{"begin":484,"end":492},"obj":"Species"},{"id":"2062","span":{"begin":748,"end":758},"obj":"Species"},{"id":"2063","span":{"begin":164,"end":172},"obj":"Chemical"},{"id":"2064","span":{"begin":294,"end":302},"obj":"Disease"},{"id":"2065","span":{"begin":643,"end":660},"obj":"Disease"},{"id":"2066","span":{"begin":843,"end":854},"obj":"Disease"},{"id":"2067","span":{"begin":859,"end":867},"obj":"Disease"},{"id":"2068","span":{"begin":963,"end":971},"obj":"Disease"},{"id":"2069","span":{"begin":1183,"end":1191},"obj":"Disease"}],"attributes":[{"id":"A2058","pred":"tao:has_database_id","subj":"2058","obj":"Gene:823"},{"id":"A2059","pred":"tao:has_database_id","subj":"2059","obj":"Gene:824"},{"id":"A2060","pred":"tao:has_database_id","subj":"2060","obj":"Gene:3569"},{"id":"A2061","pred":"tao:has_database_id","subj":"2061","obj":"Tax:694009"},{"id":"A2062","pred":"tao:has_database_id","subj":"2062","obj":"Tax:2697049"},{"id":"A2064","pred":"tao:has_database_id","subj":"2064","obj":"MESH:D005355"},{"id":"A2065","pred":"tao:has_database_id","subj":"2065","obj":"MESH:C000657245"},{"id":"A2066","pred":"tao:has_database_id","subj":"2066","obj":"MESH:D055370"},{"id":"A2067","pred":"tao:has_database_id","subj":"2067","obj":"MESH:D005355"},{"id":"A2068","pred":"tao:has_database_id","subj":"2068","obj":"MESH:D005355"},{"id":"A2069","pred":"tao:has_database_id","subj":"2069","obj":"MESH:C000657245"},{"subj":"2058","pred":"source","obj":"LitCovid-PubTator"},{"subj":"2059","pred":"source","obj":"LitCovid-PubTator"},{"subj":"2060","pred":"source","obj":"LitCovid-PubTator"},{"subj":"2061","pred":"source","obj":"LitCovid-PubTator"},{"subj":"2062","pred":"source","obj":"LitCovid-PubTator"},{"subj":"2063","pred":"source","obj":"LitCovid-PubTator"},{"subj":"2064","pred":"source","obj":"LitCovid-PubTator"},{"subj":"2065","pred":"source","obj":"LitCovid-PubTator"},{"subj":"2066","pred":"source","obj":"LitCovid-PubTator"},{"subj":"2067","pred":"source","obj":"LitCovid-PubTator"},{"subj":"2068","pred":"source","obj":"LitCovid-PubTator"},{"subj":"2069","pred":"source","obj":"LitCovid-PubTator"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"LitCovid-PD-FMA-UBERON","color":"#93eccd","default":true},{"id":"LitCovid-PD-UBERON","color":"#ecb393"},{"id":"LitCovid-PD-MONDO","color":"#9993ec"},{"id":"LitCovid-PD-CLO","color":"#a6ec93"},{"id":"LitCovid-PD-CHEBI","color":"#ec93c0"},{"id":"LitCovid-PD-GO-BP","color":"#93daec"},{"id":"LitCovid-sentences","color":"#ece393"},{"id":"LitCovid-PubTator","color":"#c993ec"}]}]}}