Publication Information

{'id': 'https://openalex.org/W1917100749', 'doi': 'https://doi.org/10.1124/dmd.115.067181', 'title': 'Elucidating the Mechanisms of Formation for Two Unusual Cytochrome P450–Mediated Fused Ring Metabolites of GDC-0623, a MAPK/ERK Kinase Inhibitor', 'display_name': 'Elucidating the Mechanisms of Formation for Two Unusual Cytochrome P450–Mediated Fused Ring Metabolites of GDC-0623, a MAPK/ERK Kinase Inhibitor', 'publication_year': 2015, 'publication_date': '2015-10-05', 'ids': {'openalex': 'https://openalex.org/W1917100749', 'doi': 'https://doi.org/10.1124/dmd.115.067181', 'mag': '1917100749', 'pmid': 'https://pubmed.ncbi.nlm.nih.gov/26438627'}, 'language': 'en', 'primary_location': {'is_oa': True, 'landing_page_url': 'https://doi.org/10.1124/dmd.115.067181', 'pdf_url': None, 'source': {'id': 'https://openalex.org/S145039780', 'display_name': 'Drug Metabolism and Disposition', 'issn_l': '0090-9556', 'issn': ['0090-9556', '1521-009X'], 'is_oa': False, 'is_in_doaj': False, 'is_core': True, 'host_organization': 'https://openalex.org/P4310316283', 'host_organization_name': 'American Society for Pharmacology and Experimental Therapeutics', 'host_organization_lineage': ['https://openalex.org/P4310316283'], 'host_organization_lineage_names': ['American Society for Pharmacology and Experimental Therapeutics'], 'type': 'journal'}, 'license': None, 'license_id': None, 'version': 'publishedVersion', 'is_accepted': True, 'is_published': True}, 'type': 'article', 'type_crossref': 'journal-article', 'indexed_in': ['crossref', 'pubmed'], 'open_access': {'is_oa': True, 'oa_status': 'bronze', 'oa_url': 'https://doi.org/10.1124/dmd.115.067181', 'any_repository_has_fulltext': False}, 'authorships': [{'author_position': 'first', 'author': {'id': 'https://openalex.org/A5064928889', 'display_name': 'Ryan Takahashi', 'orcid': 'https://orcid.org/0000-0003-1016-0633'}, 'institutions': [], 'countries': ['US'], 'is_corresponding': False, 'raw_author_name': 'Ryan H. Takahashi', 'raw_affiliation_strings': ['Departments of Drug Metabolism and Pharmacokinetics (R.H.T., S.M., Q.Y., E.F.C., S.C.K.) and Small Molecule Pharmaceutical Sciences (S.J.R.), Genentech, Inc., South San Francisco, California'], 'affiliations': [{'raw_affiliation_string': 'Departments of Drug Metabolism and Pharmacokinetics (R.H.T., S.M., Q.Y., E.F.C., S.C.K.) and Small Molecule Pharmaceutical Sciences (S.J.R.), Genentech, Inc., South San Francisco, California', 'institution_ids': []}]}, {'author_position': 'middle', 'author': {'id': 'https://openalex.org/A5111731989', 'display_name': 'Shuguang Ma', 'orcid': None}, 'institutions': [], 'countries': ['US'], 'is_corresponding': False, 'raw_author_name': 'Shuguang Ma', 'raw_affiliation_strings': ['Departments of Drug Metabolism and Pharmacokinetics (R.H.T., S.M., Q.Y., E.F.C., S.C.K.) and Small Molecule Pharmaceutical Sciences (S.J.R.), Genentech, Inc., South San Francisco, California'], 'affiliations': [{'raw_affiliation_string': 'Departments of Drug Metabolism and Pharmacokinetics (R.H.T., S.M., Q.Y., E.F.C., S.C.K.) and Small Molecule Pharmaceutical Sciences (S.J.R.), Genentech, Inc., South San Francisco, California', 'institution_ids': []}]}, {'author_position': 'middle', 'author': {'id': 'https://openalex.org/A5102925964', 'display_name': 'Sarah J. Robinson', 'orcid': None}, 'institutions': [], 'countries': ['US'], 'is_corresponding': False, 'raw_author_name': 'Sarah J. Robinson', 'raw_affiliation_strings': ['Departments of Drug Metabolism and Pharmacokinetics (R.H.T., S.M., Q.Y., E.F.C., S.C.K.) and Small Molecule Pharmaceutical Sciences (S.J.R.), Genentech, Inc., South San Francisco, California'], 'affiliations': [{'raw_affiliation_string': 'Departments of Drug Metabolism and Pharmacokinetics (R.H.T., S.M., Q.Y., E.F.C., S.C.K.) and Small Molecule Pharmaceutical Sciences (S.J.R.), Genentech, Inc., South San Francisco, California', 'institution_ids': []}]}, {'author_position': 'middle', 'author': {'id': 'https://openalex.org/A5100573524', 'display_name': 'Qin Yue', 'orcid': None}, 'institutions': [], 'countries': ['US'], 'is_corresponding': False, 'raw_author_name': 'Qin Yue', 'raw_affiliation_strings': ['Departments of Drug Metabolism and Pharmacokinetics (R.H.T., S.M., Q.Y., E.F.C., S.C.K.) and Small Molecule Pharmaceutical Sciences (S.J.R.), Genentech, Inc., South San Francisco, California'], 'affiliations': [{'raw_affiliation_string': 'Departments of Drug Metabolism and Pharmacokinetics (R.H.T., S.M., Q.Y., E.F.C., S.C.K.) and Small Molecule Pharmaceutical Sciences (S.J.R.), Genentech, Inc., South San Francisco, California', 'institution_ids': []}]}, {'author_position': 'middle', 'author': {'id': 'https://openalex.org/A5027966349', 'display_name': 'Edna F. Choo', 'orcid': 'https://orcid.org/0000-0003-4200-8302'}, 'institutions': [], 'countries': ['US'], 'is_corresponding': False, 'raw_author_name': 'Edna F. Choo', 'raw_affiliation_strings': ['Departments of Drug Metabolism and Pharmacokinetics (R.H.T., S.M., Q.Y., E.F.C., S.C.K.) and Small Molecule Pharmaceutical Sciences (S.J.R.), Genentech, Inc., South San Francisco, California'], 'affiliations': [{'raw_affiliation_string': 'Departments of Drug Metabolism and Pharmacokinetics (R.H.T., S.M., Q.Y., E.F.C., S.C.K.) and Small Molecule Pharmaceutical Sciences (S.J.R.), Genentech, Inc., South San Francisco, California', 'institution_ids': []}]}, {'author_position': 'last', 'author': {'id': 'https://openalex.org/A5030865863', 'display_name': 'S. Cyrus Khojasteh', 'orcid': 'https://orcid.org/0000-0002-8385-9288'}, 'institutions': [], 'countries': ['US'], 'is_corresponding': False, 'raw_author_name': 'S. Cyrus Khojasteh', 'raw_affiliation_strings': ['Departments of Drug Metabolism and Pharmacokinetics (R.H.T., S.M., Q.Y., E.F.C., S.C.K.) and Small Molecule Pharmaceutical Sciences (S.J.R.), Genentech, Inc., South San Francisco, California'], 'affiliations': [{'raw_affiliation_string': 'Departments of Drug Metabolism and Pharmacokinetics (R.H.T., S.M., Q.Y., E.F.C., S.C.K.) and Small Molecule Pharmaceutical Sciences (S.J.R.), Genentech, Inc., South San Francisco, California', 'institution_ids': []}]}], 'institution_assertions': [], 'countries_distinct_count': 1, 'institutions_distinct_count': 0, 'corresponding_author_ids': [], 'corresponding_institution_ids': [], 'apc_list': None, 'apc_paid': None, 'fwci': 0.144, 'has_fulltext': True, 'fulltext_origin': 'ngrams', 'cited_by_count': 7, 'citation_normalized_percentile': {'value': 0.679452, 'is_in_top_1_percent': False, 'is_in_top_10_percent': False}, 'cited_by_percentile_year': {'min': 83, 'max': 84}, 'biblio': {'volume': '43', 'issue': '12', 'first_page': '1929', 'last_page': '1933'}, 'is_retracted': False, 'is_paratext': False, 'primary_topic': {'id': 'https://openalex.org/T12318', 'display_name': 'Quinazolinone synthesis and applications', 'score': 0.9986, 'subfield': {'id': 'https://openalex.org/subfields/1605', 'display_name': 'Organic Chemistry'}, 'field': {'id': 'https://openalex.org/fields/16', 'display_name': 'Chemistry'}, 'domain': {'id': 'https://openalex.org/domains/3', 'display_name': 'Physical Sciences'}}, 'topics': [{'id': 'https://openalex.org/T12318', 'display_name': 'Quinazolinone synthesis and applications', 'score': 0.9986, 'subfield': {'id': 'https://openalex.org/subfields/1605', 'display_name': 'Organic Chemistry'}, 'field': {'id': 'https://openalex.org/fields/16', 'display_name': 'Chemistry'}, 'domain': {'id': 'https://openalex.org/domains/3', 'display_name': 'Physical Sciences'}}, {'id': 'https://openalex.org/T11533', 'display_name': 'Melanoma and MAPK Pathways', 'score': 0.9973, 'subfield': {'id': 'https://openalex.org/subfields/1312', 'display_name': 'Molecular Biology'}, 'field': {'id': 'https://openalex.org/fields/13', 'display_name': 'Biochemistry, Genetics and Molecular Biology'}, 'domain': {'id': 'https://openalex.org/domains/1', 'display_name': 'Life Sciences'}}, {'id': 'https://openalex.org/T10252', 'display_name': 'Microbial Natural Products and Biosynthesis', 'score': 0.9966, 'subfield': {'id': 'https://openalex.org/subfields/2736', 'display_name': 'Pharmacology'}, 'field': {'id': 'https://openalex.org/fields/27', 'display_name': 'Medicine'}, 'domain': {'id': 'https://openalex.org/domains/4', 'display_name': 'Health Sciences'}}], 'keywords': [{'id': 'https://openalex.org/keywords/amide', 'display_name': 'Amide', 'score': 0.4927831}, {'id': 'https://openalex.org/keywords/peptide-bond', 'display_name': 'Peptide bond', 'score': 0.4114494}], 'concepts': [{'id': 'https://openalex.org/C185592680', 'wikidata': 'https://www.wikidata.org/wiki/Q2329', 'display_name': 'Chemistry', 'level': 0, 'score': 0.7549323}, {'id': 'https://openalex.org/C2777477808', 'wikidata': 'https://www.wikidata.org/wiki/Q407595', 'display_name': 'Metabolite', 'level': 2, 'score': 0.6870906}, {'id': 'https://openalex.org/C71240020', 'wikidata': 'https://www.wikidata.org/wiki/Q186011', 'display_name': 'Stereochemistry', 'level': 1, 'score': 0.65311503}, {'id': 'https://openalex.org/C2778439535', 'wikidata': 'https://www.wikidata.org/wiki/Q188777', 'display_name': 'Amide', 'level': 2, 'score': 0.4927831}, {'id': 'https://openalex.org/C184235292', 'wikidata': 'https://www.wikidata.org/wiki/Q421851', 'display_name': 'Kinase', 'level': 2, 'score': 0.46568054}, {'id': 'https://openalex.org/C526171541', 'wikidata': 'https://www.wikidata.org/wiki/Q407693', 'display_name': 'Cytochrome P450', 'level': 3, 'score': 0.45255223}, {'id': 'https://openalex.org/C57074206', 'wikidata': 'https://www.wikidata.org/wiki/Q14197552', 'display_name': 'MAPK/ERK pathway', 'level': 3, 'score': 0.41553217}, {'id': 'https://openalex.org/C31684184', 'wikidata': 'https://www.wikidata.org/wiki/Q33293', 'display_name': 'Peptide bond', 'level': 3, 'score': 0.4114494}, {'id': 'https://openalex.org/C55493867', 'wikidata': 'https://www.wikidata.org/wiki/Q7094', 'display_name': 'Biochemistry', 'level': 1, 'score': 0.28078082}, {'id': 'https://openalex.org/C62231903', 'wikidata': 'https://www.wikidata.org/wiki/Q1057', 'display_name': 'Metabolism', 'level': 2, 'score': 0.24910119}, {'id': 'https://openalex.org/C181199279', 'wikidata': 'https://www.wikidata.org/wiki/Q8047', 'display_name': 'Enzyme', 'level': 2, 'score': 0.24488604}], 'mesh': [{'descriptor_ui': 'D003577', 'descriptor_name': 'Cytochrome P-450 Enzyme System', 'qualifier_ui': 'Q000502', 'qualifier_name': 'physiology', 'is_major_topic': True}, {'descriptor_ui': 'D020935', 'descriptor_name': 'MAP Kinase Signaling System', 'qualifier_ui': 'Q000502', 'qualifier_name': 'physiology', 'is_major_topic': True}, {'descriptor_ui': 'D020929', 'descriptor_name': 'Mitogen-Activated Protein Kinase Kinases', 'qualifier_ui': 'Q000037', 'qualifier_name': 'antagonists & inhibitors', 'is_major_topic': True}, {'descriptor_ui': 'D020929', 'descriptor_name': 'Mitogen-Activated Protein Kinase Kinases', 'qualifier_ui': 'Q000378', 'qualifier_name': 'metabolism', 'is_major_topic': True}, {'descriptor_ui': 'D047428', 'descriptor_name': 'Protein Kinase Inhibitors', 'qualifier_ui': 'Q000378', 'qualifier_name': 'metabolism', 'is_major_topic': True}, {'descriptor_ui': 'D047428', 'descriptor_name': 'Protein Kinase Inhibitors', 'qualifier_ui': 'Q000737', 'qualifier_name': 'chemistry', 'is_major_topic': True}, {'descriptor_ui': 'D000818', 'descriptor_name': 'Animals', 'qualifier_ui': '', 'qualifier_name': None, 'is_major_topic': False}, {'descriptor_ui': 'D003577', 'descriptor_name': 'Cytochrome P-450 Enzyme System', 'qualifier_ui': '', 'qualifier_name': None, 'is_major_topic': False}, {'descriptor_ui': 'D004285', 'descriptor_name': 'Dogs', 'qualifier_ui': '', 'qualifier_name': None, 'is_major_topic': False}, {'descriptor_ui': 'D005260', 'descriptor_name': 'Female', 'qualifier_ui': '', 'qualifier_name': None, 'is_major_topic': False}, {'descriptor_ui': 'D006801', 'descriptor_name': 'Humans', 'qualifier_ui': '', 'qualifier_name': None, 'is_major_topic': False}, {'descriptor_ui': 'D020935', 'descriptor_name': 'MAP Kinase Signaling System', 'qualifier_ui': 'Q000187', 'qualifier_name': 'drug effects', 'is_major_topic': False}, {'descriptor_ui': 'D020935', 'descriptor_name': 'MAP Kinase Signaling System', 'qualifier_ui': '', 'qualifier_name': None, 'is_major_topic': False}, {'descriptor_ui': 'D008297', 'descriptor_name': 'Male', 'qualifier_ui': '', 'qualifier_name': None, 'is_major_topic': False}, {'descriptor_ui': 'D008862', 'descriptor_name': 'Microsomes, Liver', 'qualifier_ui': 'Q000378', 'qualifier_name': 'metabolism', 'is_major_topic': False}, {'descriptor_ui': 'D008862', 'descriptor_name': 'Microsomes, Liver', 'qualifier_ui': 'Q000187', 'qualifier_name': 'drug effects', 'is_major_topic': False}, {'descriptor_ui': 'D008862', 'descriptor_name': 'Microsomes, Liver', 'qualifier_ui': '', 'qualifier_name': None, 'is_major_topic': False}, {'descriptor_ui': 'D020929', 'descriptor_name': 'Mitogen-Activated Protein Kinase Kinases', 'qualifier_ui': '', 'qualifier_name': None, 'is_major_topic': False}, {'descriptor_ui': 'D047428', 'descriptor_name': 'Protein Kinase Inhibitors', 'qualifier_ui': 'Q000494', 'qualifier_name': 'pharmacology', 'is_major_topic': False}, {'descriptor_ui': 'D047428', 'descriptor_name': 'Protein Kinase Inhibitors', 'qualifier_ui': '', 'qualifier_name': None, 'is_major_topic': False}, {'descriptor_ui': 'D051381', 'descriptor_name': 'Rats', 'qualifier_ui': '', 'qualifier_name': None, 'is_major_topic': False}], 'locations_count': 2, 'locations': [{'is_oa': True, 'landing_page_url': 'https://doi.org/10.1124/dmd.115.067181', 'pdf_url': None, 'source': {'id': 'https://openalex.org/S145039780', 'display_name': 'Drug Metabolism and Disposition', 'issn_l': '0090-9556', 'issn': ['0090-9556', '1521-009X'], 'is_oa': False, 'is_in_doaj': False, 'is_core': True, 'host_organization': 'https://openalex.org/P4310316283', 'host_organization_name': 'American Society for Pharmacology and Experimental Therapeutics', 'host_organization_lineage': ['https://openalex.org/P4310316283'], 'host_organization_lineage_names': ['American Society for Pharmacology and Experimental Therapeutics'], 'type': 'journal'}, 'license': None, 'license_id': None, 'version': 'publishedVersion', 'is_accepted': True, 'is_published': True}, {'is_oa': False, 'landing_page_url': 'https://pubmed.ncbi.nlm.nih.gov/26438627', 'pdf_url': None, 'source': {'id': 'https://openalex.org/S4306525036', 'display_name': 'PubMed', 'issn_l': None, 'issn': None, 'is_oa': False, 'is_in_doaj': False, 'is_core': False, 'host_organization': 'https://openalex.org/I1299303238', 'host_organization_name': 'National Institutes of Health', 'host_organization_lineage': ['https://openalex.org/I1299303238'], 'host_organization_lineage_names': ['National Institutes of Health'], 'type': 'repository'}, 'license': None, 'license_id': None, 'version': None, 'is_accepted': False, 'is_published': False}], 'best_oa_location': {'is_oa': True, 'landing_page_url': 'https://doi.org/10.1124/dmd.115.067181', 'pdf_url': None, 'source': {'id': 'https://openalex.org/S145039780', 'display_name': 'Drug Metabolism and Disposition', 'issn_l': '0090-9556', 'issn': ['0090-9556', '1521-009X'], 'is_oa': False, 'is_in_doaj': False, 'is_core': True, 'host_organization': 'https://openalex.org/P4310316283', 'host_organization_name': 'American Society for Pharmacology and Experimental Therapeutics', 'host_organization_lineage': ['https://openalex.org/P4310316283'], 'host_organization_lineage_names': ['American Society for Pharmacology and Experimental Therapeutics'], 'type': 'journal'}, 'license': None, 'license_id': None, 'version': 'publishedVersion', 'is_accepted': True, 'is_published': True}, 'sustainable_development_goals': [], 'grants': [], 'datasets': [], 'versions': [], 'referenced_works_count': 14, 'referenced_works': ['https://openalex.org/W1566258198', 'https://openalex.org/W1978183888', 'https://openalex.org/W1988733714', 'https://openalex.org/W1993006993', 'https://openalex.org/W2026231337', 'https://openalex.org/W2044433744', 'https://openalex.org/W2047259762', 'https://openalex.org/W2090758883', 'https://openalex.org/W2117819606', 'https://openalex.org/W2118666253', 'https://openalex.org/W2131274993', 'https://openalex.org/W2155421119', 'https://openalex.org/W2256006024', 'https://openalex.org/W2332578363'], 'related_works': ['https://openalex.org/W2914310478', 'https://openalex.org/W2809149148', 'https://openalex.org/W2548072374', 'https://openalex.org/W2521903434', 'https://openalex.org/W2465933703', 'https://openalex.org/W2301966358', 'https://openalex.org/W2121019104', 'https://openalex.org/W2050312203', 'https://openalex.org/W2003068062', 'https://openalex.org/W1929109117'], 'abstract_inverted_index': {'Two': [0], 'isomeric': [1], 'metabolites': [2, 44], 'of': [3, 140, 152, 190, 207], 'GDC-0623': [4, 129, 170], '[5-((2-fluoro-4-iodophenyl)amino)-N-(2-hydroxyethoxy)imidazo[1,5-a]pyridine-6-carboxamide],': [5], 'a': [6, 47, 80, 104, 177, 181, 212], 'mitogen-activated': [7], 'protein': [8], 'kinase/extracellular': [9], 'signal-regulated': [10], 'kinase': [11, 13], '(MAPK/ERK)': [12], 'inhibitor,': [14], 'were': [15, 31, 118], 'identified': [16], 'in': [17, 22, 28, 34], 'radiolabeled': [18], 'mass': [19], 'balance': [20], 'studies': [21], 'rats': [23], 'and': [24, 30, 68, 92, 112, 122, 130, 148, 167, 202], 'dogs': [25], '(approximately': [26], '5%': [27], 'excreta)': [29], 'also': [32], 'observed': [33], 'human': [35], 'circulation': [36], '(nonradiolabeled).': [37], 'Mass': [38], 'spectrometric': [39], 'data': [40], 'indicated': [41], 'that': [42, 107, 133, 176], 'both': [43], 'had': [45], 'formed': [46, 161, 180], 'new': [48], 'ring': [49, 82], 'structure': [50], 'fused': [51], 'to': [52, 63, 199], 'the': [53, 70, 76, 90, 95, 141, 153, 163, 187, 191, 196, 200], 'imidazopyridine': [54, 192], 'core.': [55], 'Given': [56], 'their': [57, 65, 73], 'unusual': [58], 'structures,': [59], 'we': [60, 131], 'conducted': [61], 'experiments': [62], 'elucidate': [64], 'chemical': [66], 'structures': [67], 'understand': [69], 'mechanisms': [71], 'for': [72, 174], 'formation.': [74, 115], 'For': [75, 94], 'first': [77], 'metabolite,': [78, 97], 'M14,': [79], 'pyrazol-3-ol': [81], 'was': [83, 101, 125, 136], 'generated': [84, 102, 126], 'by': [85, 103, 120, 144, 216], 'N-N': [86], 'bond': [87, 110, 114], 'formation': [88, 135], 'between': [89], 'aniline': [91], 'hydroxamate.': [93], 'second': [96], 'M13,': [98], 'an': [99], 'imidazol-2-one': [100], 'Hofmann-type': [105], 'rearrangement': [106, 189], 'involved': [108], 'C-C': [109], 'cleavage': [111], 'C-N': [113], 'Both': [116], 'reactions': [117], 'catalyzed': [119], 'CYP2C9': [121], 'CYP2C19.': [123], 'M14': [124], 'directly': [127], 'from': [128, 162, 169, 195], 'speculate': [132], 'its': [134], 'via': [137], 'oxidative': [138], 'activation': [139], 'hydroxamic': [142], 'ester': [143, 154], 'cytochrome': [145], 'P450': [146, 217], '(P450)': [147], 'intramolecular': [149], 'nucleophilic': [150], 'displacement': [151], 'side': [155], 'chain.': [156], 'M13': [157, 175], '(the': [158], 'rearranged': [159], 'metabolite)': [160], 'N-reduced': [164], 'hydroxamate': [165], '(amide)': [166], 'not': [168], 'directly.': [171], 'We': [172], 'propose': [173], 'P450-mediated': [178], 'reaction': [179], 'cationic': [182], 'amide': [183, 197], 'intermediate,': [184], 'which': [185], 'enabled': [186], 'molecular': [188], 'core': [193], 'migrating': [194], 'carbon': [198], 'nitrogen': [201], 'subsequent': [203], 'cyclization': [204], 'reaction.': [205], 'Each': [206], 'these': [208], 'metabolic': [209], 'pathways': [210], 'constitutes': [211], 'novel': [213], 'biotransformation': [214], 'mediated': [215], 'enzymes.': [218]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W1917100749', 'counts_by_year': [{'year': 2023, 'cited_by_count': 1}, {'year': 2022, 'cited_by_count': 1}, {'year': 2021, 'cited_by_count': 1}, {'year': 2020, 'cited_by_count': 2}, {'year': 2016, 'cited_by_count': 1}], 'updated_date': '2024-12-07T16:10:05.416822', 'created_date': '2016-06-24'}