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Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents
Inspired by the potent inhibition activity of the c-Met (mesenchymal-epithelial transition factor) inhibitor Tepotinib, a series of new Tepotinib derivatives were synthesized and evaluated for their ability to act as antiproliferative agents to find the leading compounds with good activity and limit...
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| Published in: | Molecules (Basel, Switzerland) Switzerland), 2019-03, Vol.24 (6), p.1173 |
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| Main Authors: | , , , , |
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| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c493t-114f56bb5320c7e479902be8f4f6d214adcbb0fd3ddc4489b17413df85a333c33 |
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| cites | cdi_FETCH-LOGICAL-c493t-114f56bb5320c7e479902be8f4f6d214adcbb0fd3ddc4489b17413df85a333c33 |
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| container_issue | 6 |
| container_start_page | 1173 |
| container_title | Molecules (Basel, Switzerland) |
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| creator | Zhang, Niu-Niu An, Bai-Jiao Zhou, Yan Li, Xing-Shu Yan, Ming |
| description | Inspired by the potent inhibition activity of the c-Met (mesenchymal-epithelial transition factor) inhibitor Tepotinib, a series of new Tepotinib derivatives were synthesized and evaluated for their ability to act as antiproliferative agents to find the leading compounds with good activity and limited side effects. Among them, compound
exhibited potent antiproliferative activity (IC
(50% inhibitory concentration) = 0.026 μΜ) against hepatic carcinoma 97H (human liver cancer cell) cells and, importantly, had very low inhibitory activity against normal cells. A mechanism study demonstrated that
induced G1 phase (First growth phase or G indicating gap) arrest, inhibited the phosphorylation of c-Met and its downstream signaling component, Akt (Protein Kinase B), and also inhibited the migration of hepatic carcinoma 97H cells. |
| doi_str_mv | 10.3390/molecules24061173 |
| format | article |
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exhibited potent antiproliferative activity (IC
(50% inhibitory concentration) = 0.026 μΜ) against hepatic carcinoma 97H (human liver cancer cell) cells and, importantly, had very low inhibitory activity against normal cells. A mechanism study demonstrated that
induced G1 phase (First growth phase or G indicating gap) arrest, inhibited the phosphorylation of c-Met and its downstream signaling component, Akt (Protein Kinase B), and also inhibited the migration of hepatic carcinoma 97H cells.</description><identifier>ISSN: 1420-3049</identifier><identifier>EISSN: 1420-3049</identifier><identifier>DOI: 10.3390/molecules24061173</identifier><identifier>PMID: 30934578</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>97H cells ; Acids ; AKT protein ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; antiproliferative agents ; Antiproliferatives ; Binding sites ; c-Met inhibitor ; Cell adhesion & migration ; Cell cycle ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Chemistry Techniques, Synthetic ; G1 phase ; Gene amplification ; Hepatocytes ; Humans ; Kinases ; Liver cancer ; low toxicity ; Medical prognosis ; Mesenchyme ; Nitrogen ; Phosphorylation ; Proto-Oncogene Proteins c-akt - metabolism ; Proto-Oncogene Proteins c-met - metabolism ; Signal Transduction - drug effects ; Structure-Activity Relationship</subject><ispartof>Molecules (Basel, Switzerland), 2019-03, Vol.24 (6), p.1173</ispartof><rights>2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-114f56bb5320c7e479902be8f4f6d214adcbb0fd3ddc4489b17413df85a333c33</citedby><cites>FETCH-LOGICAL-c493t-114f56bb5320c7e479902be8f4f6d214adcbb0fd3ddc4489b17413df85a333c33</cites><orcidid>0000-0002-1763-4398 ; 0000-0001-9888-0744</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2548931421/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2548931421?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30934578$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Niu-Niu</creatorcontrib><creatorcontrib>An, Bai-Jiao</creatorcontrib><creatorcontrib>Zhou, Yan</creatorcontrib><creatorcontrib>Li, Xing-Shu</creatorcontrib><creatorcontrib>Yan, Ming</creatorcontrib><title>Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents</title><title>Molecules (Basel, Switzerland)</title><addtitle>Molecules</addtitle><description>Inspired by the potent inhibition activity of the c-Met (mesenchymal-epithelial transition factor) inhibitor Tepotinib, a series of new Tepotinib derivatives were synthesized and evaluated for their ability to act as antiproliferative agents to find the leading compounds with good activity and limited side effects. Among them, compound
exhibited potent antiproliferative activity (IC
(50% inhibitory concentration) = 0.026 μΜ) against hepatic carcinoma 97H (human liver cancer cell) cells and, importantly, had very low inhibitory activity against normal cells. A mechanism study demonstrated that
induced G1 phase (First growth phase or G indicating gap) arrest, inhibited the phosphorylation of c-Met and its downstream signaling component, Akt (Protein Kinase B), and also inhibited the migration of hepatic carcinoma 97H cells.</description><subject>97H cells</subject><subject>Acids</subject><subject>AKT protein</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>antiproliferative agents</subject><subject>Antiproliferatives</subject><subject>Binding sites</subject><subject>c-Met inhibitor</subject><subject>Cell adhesion & migration</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemistry Techniques, Synthetic</subject><subject>G1 phase</subject><subject>Gene amplification</subject><subject>Hepatocytes</subject><subject>Humans</subject><subject>Kinases</subject><subject>Liver cancer</subject><subject>low toxicity</subject><subject>Medical prognosis</subject><subject>Mesenchyme</subject><subject>Nitrogen</subject><subject>Phosphorylation</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Proto-Oncogene Proteins c-met - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Structure-Activity Relationship</subject><issn>1420-3049</issn><issn>1420-3049</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNplUsFuEzEQtRCItoEP4IIscemhAXvHu44vSFEpUKnAoeVsee3ZxNGuHezdoPx9TVOqFnyxNX7vad68IeQNZ-8BFPswxB7t1GOuBGs4l_CMHHNRsTkwoZ4_eh-Rk5w3jFVc8PolOQKmQNRycUzs9T6Ma8w-n9GLneknM_oYzqgJjn5DuzbB54Fej5Pb09jR7_ib3uA2jj74ln7C5HeFsMNMTabLMPptir3vMN1V6XKFYcyvyIvO9Blf398z8vPzxc351_nVjy-X58uruRUKxjnnoqubtq2hYlaikEqxqsVFJ7rGlc6Ns23LOgfOWSEWquVScHDdojYAYAFm5PKg66LZ6G3yg0l7HY3Xd4WYVtqk0dseNRpsRTlKKiOkAyWltGyBXFgBoojNyMeD1nZqB3S2-EimfyL69Cf4tV7FnW6EZFLVReD0XiDFXxPmUQ8-W-x7EzBOWVdVSUOpumkK9N0_0E2cUiij0lVdjELJkRcUP6Bsijkn7B6a4Uz_WQf93zoUztvHLh4Yf_OHWwsms9I</recordid><startdate>20190325</startdate><enddate>20190325</enddate><creator>Zhang, Niu-Niu</creator><creator>An, Bai-Jiao</creator><creator>Zhou, Yan</creator><creator>Li, Xing-Shu</creator><creator>Yan, Ming</creator><general>MDPI AG</general><general>MDPI</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-1763-4398</orcidid><orcidid>https://orcid.org/0000-0001-9888-0744</orcidid></search><sort><creationdate>20190325</creationdate><title>Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents</title><author>Zhang, Niu-Niu ; An, Bai-Jiao ; Zhou, Yan ; Li, Xing-Shu ; Yan, Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-114f56bb5320c7e479902be8f4f6d214adcbb0fd3ddc4489b17413df85a333c33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>97H cells</topic><topic>Acids</topic><topic>AKT protein</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>antiproliferative agents</topic><topic>Antiproliferatives</topic><topic>Binding sites</topic><topic>c-Met inhibitor</topic><topic>Cell adhesion & migration</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Chemistry Techniques, Synthetic</topic><topic>G1 phase</topic><topic>Gene amplification</topic><topic>Hepatocytes</topic><topic>Humans</topic><topic>Kinases</topic><topic>Liver cancer</topic><topic>low toxicity</topic><topic>Medical prognosis</topic><topic>Mesenchyme</topic><topic>Nitrogen</topic><topic>Phosphorylation</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Proto-Oncogene Proteins c-met - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Niu-Niu</creatorcontrib><creatorcontrib>An, Bai-Jiao</creatorcontrib><creatorcontrib>Zhou, Yan</creatorcontrib><creatorcontrib>Li, Xing-Shu</creatorcontrib><creatorcontrib>Yan, Ming</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Molecules (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Niu-Niu</au><au>An, Bai-Jiao</au><au>Zhou, Yan</au><au>Li, Xing-Shu</au><au>Yan, Ming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents</atitle><jtitle>Molecules (Basel, Switzerland)</jtitle><addtitle>Molecules</addtitle><date>2019-03-25</date><risdate>2019</risdate><volume>24</volume><issue>6</issue><spage>1173</spage><pages>1173-</pages><issn>1420-3049</issn><eissn>1420-3049</eissn><abstract>Inspired by the potent inhibition activity of the c-Met (mesenchymal-epithelial transition factor) inhibitor Tepotinib, a series of new Tepotinib derivatives were synthesized and evaluated for their ability to act as antiproliferative agents to find the leading compounds with good activity and limited side effects. Among them, compound
exhibited potent antiproliferative activity (IC
(50% inhibitory concentration) = 0.026 μΜ) against hepatic carcinoma 97H (human liver cancer cell) cells and, importantly, had very low inhibitory activity against normal cells. A mechanism study demonstrated that
induced G1 phase (First growth phase or G indicating gap) arrest, inhibited the phosphorylation of c-Met and its downstream signaling component, Akt (Protein Kinase B), and also inhibited the migration of hepatic carcinoma 97H cells.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>30934578</pmid><doi>10.3390/molecules24061173</doi><orcidid>https://orcid.org/0000-0002-1763-4398</orcidid><orcidid>https://orcid.org/0000-0001-9888-0744</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecules (Basel, Switzerland), 2019-03, Vol.24 (6), p.1173 |
| issn | 1420-3049 1420-3049 |
| language | eng |
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| source | Open Access: PubMed Central; Publicly Available Content Database |
| subjects | 97H cells Acids AKT protein Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology antiproliferative agents Antiproliferatives Binding sites c-Met inhibitor Cell adhesion & migration Cell cycle Cell Line, Tumor Cell Movement - drug effects Cell Proliferation - drug effects Chemistry Techniques, Synthetic G1 phase Gene amplification Hepatocytes Humans Kinases Liver cancer low toxicity Medical prognosis Mesenchyme Nitrogen Phosphorylation Proto-Oncogene Proteins c-akt - metabolism Proto-Oncogene Proteins c-met - metabolism Signal Transduction - drug effects Structure-Activity Relationship |
| title | Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents |
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