Daporinad in vitro metabolite profiling via rat, dog, monkey and human liver microsomes by liquid chromatography/quadrupole‐orbitrap mass spectrometry
Rationale Daporinad is a novel and potent inhibitor of nicotinamide phosphoribosyl transferase with potential antineoplastic and antiangiogenic activities. We aimed to explore the metabolites of daporinad generated from liver microsomes and to propose metabolic pathways. Methods The metabolites were...
Gespeichert in:
| Veröffentlicht in: | Rapid communications in mass spectrometry 2021-09, Vol.35 (18), p.e9150-n/a |
|---|---|
| Hauptverfasser: | , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | n/a |
|---|---|
| container_issue | 18 |
| container_start_page | e9150 |
| container_title | Rapid communications in mass spectrometry |
| container_volume | 35 |
| creator | Qu, Shan‐Dan Liu, Guang‐Xuan |
| description | Rationale
Daporinad is a novel and potent inhibitor of nicotinamide phosphoribosyl transferase with potential antineoplastic and antiangiogenic activities. We aimed to explore the metabolites of daporinad generated from liver microsomes and to propose metabolic pathways.
Methods
The metabolites were generated by individually incubating daporinad (10 μM) with liver microsomes at 37°C for 60 min. The metabolites were identified by ultra‐high‐performance liquid chromatography/quadrupole‐orbitrap mass spectrometry (UPLC/Q‐Orbitrap‐MS) using electrospray ionization in positive ion mode. They were deduced by accurate MS and MS/MS data.
Results
In total, 16 metabolites were found and their identities were characterized. In rat, dog and human, they were minor; in monkey, M11 was the most abundant. Daporinad was metabolized mainly through N‐dealkylation, amide hydrolysis, hydrogenation, oxygenation and dehydrogenation. There was no human‐specific metabolite.
Conclusions
The current study provided an overview of the metabolism of daporinad, which is helpful in predicting in vivo metabolites and in selecting animal species for toxicology studies. |
| doi_str_mv | 10.1002/rcm.9150 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2558095694</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2558095694</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3490-e01a212c922c1adb688b46bfe8042cbd4ecd322ca88eec25b6bf73fedd111f473</originalsourceid><addsrcrecordid>eNp1kU2O1DAQhS0EYpoBiRMgS2xYTGZcTtIdL1HzKw1CQrCOynal20Mcp-1kUHYcgSXn4yS46YEdK0v1Pr3nqsfYUxCXIIS8isZfKqjFPbYCoTaFkCXcZyuhaigqUM0Ze5TSjRAAtRQP2VlZQa3WtVqxn69wDNENaLkb-K2bYuCeJtShdxPxMYbO9W7YZQl5xOmC27C74D4MX2nhOFi-nz0OvHe3FLl3JoYUPCWulzw7zM5ys4_B4xR2Ecf9cnWY0cZ5DD39-v4jRJ0jceQeU-JpJJM_kPPj8pg96LBP9OTuPWdf3rz-vH1XXH98-3778rowZaVEQQJQgjRKSgNo9bppdLXWHTWikkbbiowts4ZNQ2RkrbO2KTuyFgC6alOes-cn37zqYaY0tTdhjkOObGVdN_mEa1Vl6sWJOu6XInXtGJ3HuLQg2mMFba6gPVaQ0Wd3hrP2ZP-Bf2-egeIEfHM9Lf81aj9tP_wx_A0zEZVq</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2558095694</pqid></control><display><type>article</type><title>Daporinad in vitro metabolite profiling via rat, dog, monkey and human liver microsomes by liquid chromatography/quadrupole‐orbitrap mass spectrometry</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Qu, Shan‐Dan ; Liu, Guang‐Xuan</creator><creatorcontrib>Qu, Shan‐Dan ; Liu, Guang‐Xuan</creatorcontrib><description>Rationale
Daporinad is a novel and potent inhibitor of nicotinamide phosphoribosyl transferase with potential antineoplastic and antiangiogenic activities. We aimed to explore the metabolites of daporinad generated from liver microsomes and to propose metabolic pathways.
Methods
The metabolites were generated by individually incubating daporinad (10 μM) with liver microsomes at 37°C for 60 min. The metabolites were identified by ultra‐high‐performance liquid chromatography/quadrupole‐orbitrap mass spectrometry (UPLC/Q‐Orbitrap‐MS) using electrospray ionization in positive ion mode. They were deduced by accurate MS and MS/MS data.
Results
In total, 16 metabolites were found and their identities were characterized. In rat, dog and human, they were minor; in monkey, M11 was the most abundant. Daporinad was metabolized mainly through N‐dealkylation, amide hydrolysis, hydrogenation, oxygenation and dehydrogenation. There was no human‐specific metabolite.
Conclusions
The current study provided an overview of the metabolism of daporinad, which is helpful in predicting in vivo metabolites and in selecting animal species for toxicology studies.</description><identifier>ISSN: 0951-4198</identifier><identifier>EISSN: 1097-0231</identifier><identifier>DOI: 10.1002/rcm.9150</identifier><identifier>PMID: 34159659</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Animals ; Antiangiogenics ; Biocompatibility ; Chromatography ; Chromatography, High Pressure Liquid - methods ; Dealkylation ; Dehydrogenation ; Dogs ; Haplorhini ; Humans ; In vivo methods and tests ; Ions ; Liquid chromatography ; Liver ; Mass spectrometry ; Mass Spectrometry - methods ; Metabolites ; Microsomes, Liver - chemistry ; Monkeys ; Nicotinamide ; Oxygenation ; Positive ions ; Quadrupoles ; Rats ; Scientific imaging ; Species Specificity ; Spectroscopy ; Toxicology</subject><ispartof>Rapid communications in mass spectrometry, 2021-09, Vol.35 (18), p.e9150-n/a</ispartof><rights>2021 John Wiley & Sons Ltd</rights><rights>2021 John Wiley & Sons Ltd.</rights><rights>2021 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3490-e01a212c922c1adb688b46bfe8042cbd4ecd322ca88eec25b6bf73fedd111f473</citedby><cites>FETCH-LOGICAL-c3490-e01a212c922c1adb688b46bfe8042cbd4ecd322ca88eec25b6bf73fedd111f473</cites><orcidid>0000-0001-8748-8325</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Frcm.9150$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Frcm.9150$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34159659$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qu, Shan‐Dan</creatorcontrib><creatorcontrib>Liu, Guang‐Xuan</creatorcontrib><title>Daporinad in vitro metabolite profiling via rat, dog, monkey and human liver microsomes by liquid chromatography/quadrupole‐orbitrap mass spectrometry</title><title>Rapid communications in mass spectrometry</title><addtitle>Rapid Commun Mass Spectrom</addtitle><description>Rationale
Daporinad is a novel and potent inhibitor of nicotinamide phosphoribosyl transferase with potential antineoplastic and antiangiogenic activities. We aimed to explore the metabolites of daporinad generated from liver microsomes and to propose metabolic pathways.
Methods
The metabolites were generated by individually incubating daporinad (10 μM) with liver microsomes at 37°C for 60 min. The metabolites were identified by ultra‐high‐performance liquid chromatography/quadrupole‐orbitrap mass spectrometry (UPLC/Q‐Orbitrap‐MS) using electrospray ionization in positive ion mode. They were deduced by accurate MS and MS/MS data.
Results
In total, 16 metabolites were found and their identities were characterized. In rat, dog and human, they were minor; in monkey, M11 was the most abundant. Daporinad was metabolized mainly through N‐dealkylation, amide hydrolysis, hydrogenation, oxygenation and dehydrogenation. There was no human‐specific metabolite.
Conclusions
The current study provided an overview of the metabolism of daporinad, which is helpful in predicting in vivo metabolites and in selecting animal species for toxicology studies.</description><subject>Animals</subject><subject>Antiangiogenics</subject><subject>Biocompatibility</subject><subject>Chromatography</subject><subject>Chromatography, High Pressure Liquid - methods</subject><subject>Dealkylation</subject><subject>Dehydrogenation</subject><subject>Dogs</subject><subject>Haplorhini</subject><subject>Humans</subject><subject>In vivo methods and tests</subject><subject>Ions</subject><subject>Liquid chromatography</subject><subject>Liver</subject><subject>Mass spectrometry</subject><subject>Mass Spectrometry - methods</subject><subject>Metabolites</subject><subject>Microsomes, Liver - chemistry</subject><subject>Monkeys</subject><subject>Nicotinamide</subject><subject>Oxygenation</subject><subject>Positive ions</subject><subject>Quadrupoles</subject><subject>Rats</subject><subject>Scientific imaging</subject><subject>Species Specificity</subject><subject>Spectroscopy</subject><subject>Toxicology</subject><issn>0951-4198</issn><issn>1097-0231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU2O1DAQhS0EYpoBiRMgS2xYTGZcTtIdL1HzKw1CQrCOynal20Mcp-1kUHYcgSXn4yS46YEdK0v1Pr3nqsfYUxCXIIS8isZfKqjFPbYCoTaFkCXcZyuhaigqUM0Ze5TSjRAAtRQP2VlZQa3WtVqxn69wDNENaLkb-K2bYuCeJtShdxPxMYbO9W7YZQl5xOmC27C74D4MX2nhOFi-nz0OvHe3FLl3JoYUPCWulzw7zM5ys4_B4xR2Ecf9cnWY0cZ5DD39-v4jRJ0jceQeU-JpJJM_kPPj8pg96LBP9OTuPWdf3rz-vH1XXH98-3778rowZaVEQQJQgjRKSgNo9bppdLXWHTWikkbbiowts4ZNQ2RkrbO2KTuyFgC6alOes-cn37zqYaY0tTdhjkOObGVdN_mEa1Vl6sWJOu6XInXtGJ3HuLQg2mMFba6gPVaQ0Wd3hrP2ZP-Bf2-egeIEfHM9Lf81aj9tP_wx_A0zEZVq</recordid><startdate>20210930</startdate><enddate>20210930</enddate><creator>Qu, Shan‐Dan</creator><creator>Liu, Guang‐Xuan</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>JQ2</scope><scope>L7M</scope><orcidid>https://orcid.org/0000-0001-8748-8325</orcidid></search><sort><creationdate>20210930</creationdate><title>Daporinad in vitro metabolite profiling via rat, dog, monkey and human liver microsomes by liquid chromatography/quadrupole‐orbitrap mass spectrometry</title><author>Qu, Shan‐Dan ; Liu, Guang‐Xuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3490-e01a212c922c1adb688b46bfe8042cbd4ecd322ca88eec25b6bf73fedd111f473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Antiangiogenics</topic><topic>Biocompatibility</topic><topic>Chromatography</topic><topic>Chromatography, High Pressure Liquid - methods</topic><topic>Dealkylation</topic><topic>Dehydrogenation</topic><topic>Dogs</topic><topic>Haplorhini</topic><topic>Humans</topic><topic>In vivo methods and tests</topic><topic>Ions</topic><topic>Liquid chromatography</topic><topic>Liver</topic><topic>Mass spectrometry</topic><topic>Mass Spectrometry - methods</topic><topic>Metabolites</topic><topic>Microsomes, Liver - chemistry</topic><topic>Monkeys</topic><topic>Nicotinamide</topic><topic>Oxygenation</topic><topic>Positive ions</topic><topic>Quadrupoles</topic><topic>Rats</topic><topic>Scientific imaging</topic><topic>Species Specificity</topic><topic>Spectroscopy</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qu, Shan‐Dan</creatorcontrib><creatorcontrib>Liu, Guang‐Xuan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Rapid communications in mass spectrometry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qu, Shan‐Dan</au><au>Liu, Guang‐Xuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Daporinad in vitro metabolite profiling via rat, dog, monkey and human liver microsomes by liquid chromatography/quadrupole‐orbitrap mass spectrometry</atitle><jtitle>Rapid communications in mass spectrometry</jtitle><addtitle>Rapid Commun Mass Spectrom</addtitle><date>2021-09-30</date><risdate>2021</risdate><volume>35</volume><issue>18</issue><spage>e9150</spage><epage>n/a</epage><pages>e9150-n/a</pages><issn>0951-4198</issn><eissn>1097-0231</eissn><abstract>Rationale
Daporinad is a novel and potent inhibitor of nicotinamide phosphoribosyl transferase with potential antineoplastic and antiangiogenic activities. We aimed to explore the metabolites of daporinad generated from liver microsomes and to propose metabolic pathways.
Methods
The metabolites were generated by individually incubating daporinad (10 μM) with liver microsomes at 37°C for 60 min. The metabolites were identified by ultra‐high‐performance liquid chromatography/quadrupole‐orbitrap mass spectrometry (UPLC/Q‐Orbitrap‐MS) using electrospray ionization in positive ion mode. They were deduced by accurate MS and MS/MS data.
Results
In total, 16 metabolites were found and their identities were characterized. In rat, dog and human, they were minor; in monkey, M11 was the most abundant. Daporinad was metabolized mainly through N‐dealkylation, amide hydrolysis, hydrogenation, oxygenation and dehydrogenation. There was no human‐specific metabolite.
Conclusions
The current study provided an overview of the metabolism of daporinad, which is helpful in predicting in vivo metabolites and in selecting animal species for toxicology studies.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>34159659</pmid><doi>10.1002/rcm.9150</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-8748-8325</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0951-4198 |
| ispartof | Rapid communications in mass spectrometry, 2021-09, Vol.35 (18), p.e9150-n/a |
| issn | 0951-4198 1097-0231 |
| language | eng |
| recordid | cdi_proquest_journals_2558095694 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals Antiangiogenics Biocompatibility Chromatography Chromatography, High Pressure Liquid - methods Dealkylation Dehydrogenation Dogs Haplorhini Humans In vivo methods and tests Ions Liquid chromatography Liver Mass spectrometry Mass Spectrometry - methods Metabolites Microsomes, Liver - chemistry Monkeys Nicotinamide Oxygenation Positive ions Quadrupoles Rats Scientific imaging Species Specificity Spectroscopy Toxicology |
| title | Daporinad in vitro metabolite profiling via rat, dog, monkey and human liver microsomes by liquid chromatography/quadrupole‐orbitrap mass spectrometry |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T22%3A13%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Daporinad%20in%20vitro%20metabolite%20profiling%20via%20rat,%20dog,%20monkey%20and%20human%20liver%20microsomes%20by%20liquid%20chromatography/quadrupole%E2%80%90orbitrap%20mass%20spectrometry&rft.jtitle=Rapid%20communications%20in%20mass%20spectrometry&rft.au=Qu,%20Shan%E2%80%90Dan&rft.date=2021-09-30&rft.volume=35&rft.issue=18&rft.spage=e9150&rft.epage=n/a&rft.pages=e9150-n/a&rft.issn=0951-4198&rft.eissn=1097-0231&rft_id=info:doi/10.1002/rcm.9150&rft_dat=%3Cproquest_cross%3E2558095694%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2558095694&rft_id=info:pmid/34159659&rfr_iscdi=true |