PMC:7594251 / 128039-129328 JSONTXT

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T135","span":{"begin":697,"end":700},"obj":"Body_part"}],"attributes":[{"id":"A135","pred":"fma_id","subj":"T135","obj":"http://purl.org/sig/ont/fma/fma58066"}],"text":"Table 2 The names, structures, targets, FBDD optimization strategy used, biophysical techniques used, and status in clinical trials of select drugs derived from the FBDD approach.\nDrug (Company) Target Original Fragment(s) * Advanced Molecule and Progress in Clinical Trials Techniques Used\nVemurafenib (Plexxikon) [224,226] BRAF-V600E Approved high-concentration biochemical fragment screening, X-ray crystallography\nVenetoclax (AbbVie, Genetech) [227,228,229,230] BCL-2 Approved NMR, X-ray crystallography\nRibociclib (Novartis Europharm Limited) [231] CDK4 and 6 Information Not Available Approved Information not Available\nPLX3397 (Plexxikon) [232,233,234] FMS, KIT, and FLT3-ITD Phase 3 X-ray crystallography, Structure Confirmed by NMR, MS, and HPLC\nVerubecestat (Merck) [235,236] BACE1 Phase 3 NMR, X-ray crystallography, inhibition of cathepsin D\nOnalespib (Astex) [237,238] HSP90 Phase 2 X-ray crystallography, isothermal titration calorimetry, NMR\nAZD5099 [239,240] Topoisomerase II Phase 1 NMR, Surface Plasmon Resonance, isothermal calorimetry, X-ray cystallography\nAT7519 [241,242,243,244] CDK 1, 2, 4, and 5 Phase 2 NMR, MS, X-ray crystallography\n* Structures for some of the fragments are taken directly from Dan Erlanson’s blog at [245]."}

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T256","span":{"begin":678,"end":681},"obj":"http://purl.obolibrary.org/obo/PR_000002062"},{"id":"T257","span":{"begin":692,"end":696},"obj":"http://purl.obolibrary.org/obo/PR_000002001"},{"id":"T258","span":{"begin":763,"end":765},"obj":"http://purl.obolibrary.org/obo/CLO_0007874"},{"id":"T259","span":{"begin":1171,"end":1173},"obj":"http://purl.obolibrary.org/obo/CLO_0007874"},{"id":"T260","span":{"begin":1260,"end":1263},"obj":"http://purl.obolibrary.org/obo/CLO_0002697"}],"text":"Table 2 The names, structures, targets, FBDD optimization strategy used, biophysical techniques used, and status in clinical trials of select drugs derived from the FBDD approach.\nDrug (Company) Target Original Fragment(s) * Advanced Molecule and Progress in Clinical Trials Techniques Used\nVemurafenib (Plexxikon) [224,226] BRAF-V600E Approved high-concentration biochemical fragment screening, X-ray crystallography\nVenetoclax (AbbVie, Genetech) [227,228,229,230] BCL-2 Approved NMR, X-ray crystallography\nRibociclib (Novartis Europharm Limited) [231] CDK4 and 6 Information Not Available Approved Information not Available\nPLX3397 (Plexxikon) [232,233,234] FMS, KIT, and FLT3-ITD Phase 3 X-ray crystallography, Structure Confirmed by NMR, MS, and HPLC\nVerubecestat (Merck) [235,236] BACE1 Phase 3 NMR, X-ray crystallography, inhibition of cathepsin D\nOnalespib (Astex) [237,238] HSP90 Phase 2 X-ray crystallography, isothermal titration calorimetry, NMR\nAZD5099 [239,240] Topoisomerase II Phase 1 NMR, Surface Plasmon Resonance, isothermal calorimetry, X-ray cystallography\nAT7519 [241,242,243,244] CDK 1, 2, 4, and 5 Phase 2 NMR, MS, X-ray crystallography\n* Structures for some of the fragments are taken directly from Dan Erlanson’s blog at [245]."}

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T95431","span":{"begin":143,"end":148},"obj":"Chemical"},{"id":"T61683","span":{"begin":643,"end":650},"obj":"Chemical"},{"id":"T54879","span":{"begin":763,"end":765},"obj":"Chemical"},{"id":"T36558","span":{"begin":1019,"end":1021},"obj":"Chemical"},{"id":"T92376","span":{"begin":1110,"end":1116},"obj":"Chemical"},{"id":"T35664","span":{"begin":1171,"end":1173},"obj":"Chemical"}],"attributes":[{"id":"A22226","pred":"chebi_id","subj":"T95431","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A64030","pred":"chebi_id","subj":"T61683","obj":"http://purl.obolibrary.org/obo/CHEBI_145373"},{"id":"A31220","pred":"chebi_id","subj":"T54879","obj":"http://purl.obolibrary.org/obo/CHEBI_73613"},{"id":"A2616","pred":"chebi_id","subj":"T36558","obj":"http://purl.obolibrary.org/obo/CHEBI_74067"},{"id":"A9402","pred":"chebi_id","subj":"T92376","obj":"http://purl.obolibrary.org/obo/CHEBI_91326"},{"id":"A19966","pred":"chebi_id","subj":"T35664","obj":"http://purl.obolibrary.org/obo/CHEBI_73613"}],"text":"Table 2 The names, structures, targets, FBDD optimization strategy used, biophysical techniques used, and status in clinical trials of select drugs derived from the FBDD approach.\nDrug (Company) Target Original Fragment(s) * Advanced Molecule and Progress in Clinical Trials Techniques Used\nVemurafenib (Plexxikon) [224,226] BRAF-V600E Approved high-concentration biochemical fragment screening, X-ray crystallography\nVenetoclax (AbbVie, Genetech) [227,228,229,230] BCL-2 Approved NMR, X-ray crystallography\nRibociclib (Novartis Europharm Limited) [231] CDK4 and 6 Information Not Available Approved Information not Available\nPLX3397 (Plexxikon) [232,233,234] FMS, KIT, and FLT3-ITD Phase 3 X-ray crystallography, Structure Confirmed by NMR, MS, and HPLC\nVerubecestat (Merck) [235,236] BACE1 Phase 3 NMR, X-ray crystallography, inhibition of cathepsin D\nOnalespib (Astex) [237,238] HSP90 Phase 2 X-ray crystallography, isothermal titration calorimetry, NMR\nAZD5099 [239,240] Topoisomerase II Phase 1 NMR, Surface Plasmon Resonance, isothermal calorimetry, X-ray cystallography\nAT7519 [241,242,243,244] CDK 1, 2, 4, and 5 Phase 2 NMR, MS, X-ray crystallography\n* Structures for some of the fragments are taken directly from Dan Erlanson’s blog at [245]."}

{"project":"LitCovid-PubTator","denotations":[{"id":"2395","span":{"begin":331,"end":335},"obj":"Gene"},{"id":"2396","span":{"begin":476,"end":481},"obj":"Gene"},{"id":"2397","span":{"begin":568,"end":572},"obj":"Gene"},{"id":"2398","span":{"begin":692,"end":696},"obj":"Gene"},{"id":"2399","span":{"begin":808,"end":813},"obj":"Gene"},{"id":"2400","span":{"begin":1136,"end":1147},"obj":"Gene"},{"id":"2401","span":{"begin":908,"end":913},"obj":"Gene"},{"id":"2402","span":{"begin":354,"end":358},"obj":"Gene"},{"id":"2403","span":{"begin":336,"end":341},"obj":"Mutation"},{"id":"2405","span":{"begin":166,"end":170},"obj":"Chemical"},{"id":"2407","span":{"begin":1260,"end":1263},"obj":"Gene"}],"attributes":[{"id":"A2395","pred":"tao:has_database_id","subj":"2395","obj":"Gene:673"},{"id":"A2396","pred":"tao:has_database_id","subj":"2396","obj":"Gene:596"},{"id":"A2397","pred":"tao:has_database_id","subj":"2397","obj":"Gene:1019"},{"id":"A2398","pred":"tao:has_database_id","subj":"2398","obj":"Gene:2322"},{"id":"A2399","pred":"tao:has_database_id","subj":"2399","obj":"Gene:23621"},{"id":"A2400","pred":"tao:has_database_id","subj":"2400","obj":"Gene:983"},{"id":"A2401","pred":"tao:has_database_id","subj":"2401","obj":"Gene:3320"},{"id":"A2402","pred":"tao:has_database_id","subj":"2402","obj":"Gene:104137"},{"id":"A2403","pred":"tao:has_standard_notation","subj":"2403","obj":"rs113488022"},{"id":"A2407","pred":"tao:has_database_id","subj":"2407","obj":"Gene:4681"}],"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_"}],"text":"Table 2 The names, structures, targets, FBDD optimization strategy used, biophysical techniques used, and status in clinical trials of select drugs derived from the FBDD approach.\nDrug (Company) Target Original Fragment(s) * Advanced Molecule and Progress in Clinical Trials Techniques Used\nVemurafenib (Plexxikon) [224,226] BRAF-V600E Approved high-concentration biochemical fragment screening, X-ray crystallography\nVenetoclax (AbbVie, Genetech) [227,228,229,230] BCL-2 Approved NMR, X-ray crystallography\nRibociclib (Novartis Europharm Limited) [231] CDK4 and 6 Information Not Available Approved Information not Available\nPLX3397 (Plexxikon) [232,233,234] FMS, KIT, and FLT3-ITD Phase 3 X-ray crystallography, Structure Confirmed by NMR, MS, and HPLC\nVerubecestat (Merck) [235,236] BACE1 Phase 3 NMR, X-ray crystallography, inhibition of cathepsin D\nOnalespib (Astex) [237,238] HSP90 Phase 2 X-ray crystallography, isothermal titration calorimetry, NMR\nAZD5099 [239,240] Topoisomerase II Phase 1 NMR, Surface Plasmon Resonance, isothermal calorimetry, X-ray cystallography\nAT7519 [241,242,243,244] CDK 1, 2, 4, and 5 Phase 2 NMR, MS, X-ray crystallography\n* Structures for some of the fragments are taken directly from Dan Erlanson’s blog at [245]."}

{"project":"LitCovid-sentences","denotations":[{"id":"T895","span":{"begin":0,"end":180},"obj":"Sentence"},{"id":"T896","span":{"begin":181,"end":295},"obj":"Sentence"},{"id":"T897","span":{"begin":296,"end":426},"obj":"Sentence"},{"id":"T898","span":{"begin":427,"end":520},"obj":"Sentence"},{"id":"T899","span":{"begin":521,"end":642},"obj":"Sentence"},{"id":"T900","span":{"begin":643,"end":775},"obj":"Sentence"},{"id":"T901","span":{"begin":776,"end":878},"obj":"Sentence"},{"id":"T902","span":{"begin":879,"end":985},"obj":"Sentence"},{"id":"T903","span":{"begin":986,"end":1109},"obj":"Sentence"},{"id":"T904","span":{"begin":1110,"end":1196},"obj":"Sentence"},{"id":"T905","span":{"begin":1197,"end":1289},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Table 2 The names, structures, targets, FBDD optimization strategy used, biophysical techniques used, and status in clinical trials of select drugs derived from the FBDD approach.\nDrug (Company) Target Original Fragment(s) * Advanced Molecule and Progress in Clinical Trials Techniques Used\nVemurafenib (Plexxikon) [224,226] BRAF-V600E Approved high-concentration biochemical fragment screening, X-ray crystallography\nVenetoclax (AbbVie, Genetech) [227,228,229,230] BCL-2 Approved NMR, X-ray crystallography\nRibociclib (Novartis Europharm Limited) [231] CDK4 and 6 Information Not Available Approved Information not Available\nPLX3397 (Plexxikon) [232,233,234] FMS, KIT, and FLT3-ITD Phase 3 X-ray crystallography, Structure Confirmed by NMR, MS, and HPLC\nVerubecestat (Merck) [235,236] BACE1 Phase 3 NMR, X-ray crystallography, inhibition of cathepsin D\nOnalespib (Astex) [237,238] HSP90 Phase 2 X-ray crystallography, isothermal titration calorimetry, NMR\nAZD5099 [239,240] Topoisomerase II Phase 1 NMR, Surface Plasmon Resonance, isothermal calorimetry, X-ray cystallography\nAT7519 [241,242,243,244] CDK 1, 2, 4, and 5 Phase 2 NMR, MS, X-ray crystallography\n* Structures for some of the fragments are taken directly from Dan Erlanson’s blog at [245]."}