Inhibitors of Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (Shp2) Based on Oxindole Scaffolds
Screening of the NCI diversity set of compounds has led to the identification of 5 (NSC-117199), which inhibits the protein tyrosine phosphatase (PTP) Shp2 with an IC50 of 47 μM. A focused library incorporating an isatin scaffold was designed and evaluated for inhibition of Shp2 and Shp1 PTP activit...
Gespeichert in:
| Veröffentlicht in: | Journal of medicinal chemistry 2008-08, Vol.51 (16), p.4948-4956 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 4956 |
|---|---|
| container_issue | 16 |
| container_start_page | 4948 |
| container_title | Journal of medicinal chemistry |
| container_volume | 51 |
| creator | Lawrence, Harshani R Pireddu, Roberta Chen, Liwei Luo, Yunting Sung, Shen-Shu Szymanski, Ann Marie Yip, M. L. Richard Guida, Wayne C Sebti, Saïd M Wu, Jie Lawrence, Nicholas J |
| description | Screening of the NCI diversity set of compounds has led to the identification of 5 (NSC-117199), which inhibits the protein tyrosine phosphatase (PTP) Shp2 with an IC50 of 47 μM. A focused library incorporating an isatin scaffold was designed and evaluated for inhibition of Shp2 and Shp1 PTP activities. Several compounds were identified that selectively inhibit Shp2 over Shp1 and PTP1B with low to submicromolar activity. A model for the binding of the active compounds is proposed. |
| doi_str_mv | 10.1021/jm8002526 |
| format | Article |
| fullrecord | <record><control><sourceid>acs_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2744494</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>a177544312</sourcerecordid><originalsourceid>FETCH-LOGICAL-a537t-ec78e4bf08768ed292d2bf3db4f30f3232a43a5cb364118fc1c61ce7664fdc963</originalsourceid><addsrcrecordid>eNptkE1vEzEQhi0EoqFw4A8gX5DoYcFf6_VekCClTUulRkrganm9dtZh117ZW9T8-7pKlBaJ02hmnnln5gXgPUafMSL4y3YQCJGS8BdghkuCCiYQewlmuUgKwgk9AW9S2iKEKCb0NTjBggtEy3oGxivfucZNISYYLFxFDRdhCH3Y7AoCz8OgnIfz4Kccnd_AZQyTyaX1LobkvIHLLqSxU5NKJg98WnUjOYPfc9bC4OHtvfNt6A1caWVt6Nv0Fryyqk_m3SGegl8XP9bzRXFze3k1_3ZTqJJWU2F0JQxrLBIVF6YlNWlJY2nbMEuRpYQSxagqdUM5w1hYjTXH2lScM9vqmtNT8HWvO941g2m18VNUvRyjG1TcyaCc_LfjXSc34a8kFWOsZlngbC-g86cpGnucxUg-2i6Ptmf2w_NlT-TB5wx8PAAqadXbqLx26cgRVNaixjhzxZ5zaTL3x76KfySvaFXK9XIly_PF7_q6EvLnk67SSW7DXfTZ0_8c-ADlXqY_</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Inhibitors of Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (Shp2) Based on Oxindole Scaffolds</title><source>ACS Publications</source><source>MEDLINE</source><creator>Lawrence, Harshani R ; Pireddu, Roberta ; Chen, Liwei ; Luo, Yunting ; Sung, Shen-Shu ; Szymanski, Ann Marie ; Yip, M. L. Richard ; Guida, Wayne C ; Sebti, Saïd M ; Wu, Jie ; Lawrence, Nicholas J</creator><creatorcontrib>Lawrence, Harshani R ; Pireddu, Roberta ; Chen, Liwei ; Luo, Yunting ; Sung, Shen-Shu ; Szymanski, Ann Marie ; Yip, M. L. Richard ; Guida, Wayne C ; Sebti, Saïd M ; Wu, Jie ; Lawrence, Nicholas J</creatorcontrib><description>Screening of the NCI diversity set of compounds has led to the identification of 5 (NSC-117199), which inhibits the protein tyrosine phosphatase (PTP) Shp2 with an IC50 of 47 μM. A focused library incorporating an isatin scaffold was designed and evaluated for inhibition of Shp2 and Shp1 PTP activities. Several compounds were identified that selectively inhibit Shp2 over Shp1 and PTP1B with low to submicromolar activity. A model for the binding of the active compounds is proposed.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm8002526</identifier><identifier>PMID: 18680359</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Antineoplastic agents ; Binding Sites ; Biological and medical sciences ; General aspects ; Indoles - chemical synthesis ; Indoles - pharmacology ; Inhibitory Concentration 50 ; Medical sciences ; Models, Molecular ; Pharmacology. Drug treatments ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - antagonists & inhibitors ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 - antagonists & inhibitors ; src Homology Domains - drug effects ; Sulfonic Acids - chemical synthesis ; Sulfonic Acids - pharmacology</subject><ispartof>Journal of medicinal chemistry, 2008-08, Vol.51 (16), p.4948-4956</ispartof><rights>Copyright © 2008 American Chemical Society</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a537t-ec78e4bf08768ed292d2bf3db4f30f3232a43a5cb364118fc1c61ce7664fdc963</citedby><cites>FETCH-LOGICAL-a537t-ec78e4bf08768ed292d2bf3db4f30f3232a43a5cb364118fc1c61ce7664fdc963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm8002526$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm8002526$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,314,776,780,881,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20598911$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18680359$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lawrence, Harshani R</creatorcontrib><creatorcontrib>Pireddu, Roberta</creatorcontrib><creatorcontrib>Chen, Liwei</creatorcontrib><creatorcontrib>Luo, Yunting</creatorcontrib><creatorcontrib>Sung, Shen-Shu</creatorcontrib><creatorcontrib>Szymanski, Ann Marie</creatorcontrib><creatorcontrib>Yip, M. L. Richard</creatorcontrib><creatorcontrib>Guida, Wayne C</creatorcontrib><creatorcontrib>Sebti, Saïd M</creatorcontrib><creatorcontrib>Wu, Jie</creatorcontrib><creatorcontrib>Lawrence, Nicholas J</creatorcontrib><title>Inhibitors of Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (Shp2) Based on Oxindole Scaffolds</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Screening of the NCI diversity set of compounds has led to the identification of 5 (NSC-117199), which inhibits the protein tyrosine phosphatase (PTP) Shp2 with an IC50 of 47 μM. A focused library incorporating an isatin scaffold was designed and evaluated for inhibition of Shp2 and Shp1 PTP activities. Several compounds were identified that selectively inhibit Shp2 over Shp1 and PTP1B with low to submicromolar activity. A model for the binding of the active compounds is proposed.</description><subject>Antineoplastic agents</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>General aspects</subject><subject>Indoles - chemical synthesis</subject><subject>Indoles - pharmacology</subject><subject>Inhibitory Concentration 50</subject><subject>Medical sciences</subject><subject>Models, Molecular</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors</subject><subject>Protein Tyrosine Phosphatase, Non-Receptor Type 11 - antagonists & inhibitors</subject><subject>Protein Tyrosine Phosphatase, Non-Receptor Type 6 - antagonists & inhibitors</subject><subject>src Homology Domains - drug effects</subject><subject>Sulfonic Acids - chemical synthesis</subject><subject>Sulfonic Acids - pharmacology</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1vEzEQhi0EoqFw4A8gX5DoYcFf6_VekCClTUulRkrganm9dtZh117ZW9T8-7pKlBaJ02hmnnln5gXgPUafMSL4y3YQCJGS8BdghkuCCiYQewlmuUgKwgk9AW9S2iKEKCb0NTjBggtEy3oGxivfucZNISYYLFxFDRdhCH3Y7AoCz8OgnIfz4Kccnd_AZQyTyaX1LobkvIHLLqSxU5NKJg98WnUjOYPfc9bC4OHtvfNt6A1caWVt6Nv0Fryyqk_m3SGegl8XP9bzRXFze3k1_3ZTqJJWU2F0JQxrLBIVF6YlNWlJY2nbMEuRpYQSxagqdUM5w1hYjTXH2lScM9vqmtNT8HWvO941g2m18VNUvRyjG1TcyaCc_LfjXSc34a8kFWOsZlngbC-g86cpGnucxUg-2i6Ptmf2w_NlT-TB5wx8PAAqadXbqLx26cgRVNaixjhzxZ5zaTL3x76KfySvaFXK9XIly_PF7_q6EvLnk67SSW7DXfTZ0_8c-ADlXqY_</recordid><startdate>20080828</startdate><enddate>20080828</enddate><creator>Lawrence, Harshani R</creator><creator>Pireddu, Roberta</creator><creator>Chen, Liwei</creator><creator>Luo, Yunting</creator><creator>Sung, Shen-Shu</creator><creator>Szymanski, Ann Marie</creator><creator>Yip, M. L. Richard</creator><creator>Guida, Wayne C</creator><creator>Sebti, Saïd M</creator><creator>Wu, Jie</creator><creator>Lawrence, Nicholas J</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><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>5PM</scope></search><sort><creationdate>20080828</creationdate><title>Inhibitors of Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (Shp2) Based on Oxindole Scaffolds</title><author>Lawrence, Harshani R ; Pireddu, Roberta ; Chen, Liwei ; Luo, Yunting ; Sung, Shen-Shu ; Szymanski, Ann Marie ; Yip, M. L. Richard ; Guida, Wayne C ; Sebti, Saïd M ; Wu, Jie ; Lawrence, Nicholas J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a537t-ec78e4bf08768ed292d2bf3db4f30f3232a43a5cb364118fc1c61ce7664fdc963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Antineoplastic agents</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>General aspects</topic><topic>Indoles - chemical synthesis</topic><topic>Indoles - pharmacology</topic><topic>Inhibitory Concentration 50</topic><topic>Medical sciences</topic><topic>Models, Molecular</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors</topic><topic>Protein Tyrosine Phosphatase, Non-Receptor Type 11 - antagonists & inhibitors</topic><topic>Protein Tyrosine Phosphatase, Non-Receptor Type 6 - antagonists & inhibitors</topic><topic>src Homology Domains - drug effects</topic><topic>Sulfonic Acids - chemical synthesis</topic><topic>Sulfonic Acids - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lawrence, Harshani R</creatorcontrib><creatorcontrib>Pireddu, Roberta</creatorcontrib><creatorcontrib>Chen, Liwei</creatorcontrib><creatorcontrib>Luo, Yunting</creatorcontrib><creatorcontrib>Sung, Shen-Shu</creatorcontrib><creatorcontrib>Szymanski, Ann Marie</creatorcontrib><creatorcontrib>Yip, M. L. Richard</creatorcontrib><creatorcontrib>Guida, Wayne C</creatorcontrib><creatorcontrib>Sebti, Saïd M</creatorcontrib><creatorcontrib>Wu, Jie</creatorcontrib><creatorcontrib>Lawrence, Nicholas J</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lawrence, Harshani R</au><au>Pireddu, Roberta</au><au>Chen, Liwei</au><au>Luo, Yunting</au><au>Sung, Shen-Shu</au><au>Szymanski, Ann Marie</au><au>Yip, M. L. Richard</au><au>Guida, Wayne C</au><au>Sebti, Saïd M</au><au>Wu, Jie</au><au>Lawrence, Nicholas J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibitors of Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (Shp2) Based on Oxindole Scaffolds</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2008-08-28</date><risdate>2008</risdate><volume>51</volume><issue>16</issue><spage>4948</spage><epage>4956</epage><pages>4948-4956</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>Screening of the NCI diversity set of compounds has led to the identification of 5 (NSC-117199), which inhibits the protein tyrosine phosphatase (PTP) Shp2 with an IC50 of 47 μM. A focused library incorporating an isatin scaffold was designed and evaluated for inhibition of Shp2 and Shp1 PTP activities. Several compounds were identified that selectively inhibit Shp2 over Shp1 and PTP1B with low to submicromolar activity. A model for the binding of the active compounds is proposed.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>18680359</pmid><doi>10.1021/jm8002526</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2008-08, Vol.51 (16), p.4948-4956 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2744494 |
| source | ACS Publications; MEDLINE |
| subjects | Antineoplastic agents Binding Sites Biological and medical sciences General aspects Indoles - chemical synthesis Indoles - pharmacology Inhibitory Concentration 50 Medical sciences Models, Molecular Pharmacology. Drug treatments Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors Protein Tyrosine Phosphatase, Non-Receptor Type 11 - antagonists & inhibitors Protein Tyrosine Phosphatase, Non-Receptor Type 6 - antagonists & inhibitors src Homology Domains - drug effects Sulfonic Acids - chemical synthesis Sulfonic Acids - pharmacology |
| title | Inhibitors of Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (Shp2) Based on Oxindole Scaffolds |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T06%3A17%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-acs_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inhibitors%20of%20Src%20Homology-2%20Domain%20Containing%20Protein%20Tyrosine%20Phosphatase-2%20(Shp2)%20Based%20on%20Oxindole%20Scaffolds&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Lawrence,%20Harshani%20R&rft.date=2008-08-28&rft.volume=51&rft.issue=16&rft.spage=4948&rft.epage=4956&rft.pages=4948-4956&rft.issn=0022-2623&rft.eissn=1520-4804&rft.coden=JMCMAR&rft_id=info:doi/10.1021/jm8002526&rft_dat=%3Cacs_pubme%3Ea177544312%3C/acs_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/18680359&rfr_iscdi=true |