RapamycinFungusV1, Main, Exploration, bibRecord, 000999

Synthesis of Rapamycin Derivatives Containing the Triazole Moiety Used as Potential mTOR-Targeted Anticancer Agents.

Identifieur interne : 000999 ( Main/Exploration ); précédent : 000998; suivant : 000A00

Synthesis of Rapamycin Derivatives Containing the Triazole Moiety Used as Potential mTOR-Targeted Anticancer Agents.

Source :

Archiv der Pharmazie [ 1521-4184 ] ; 2016.

RBID : pubmed:27150260

Descripteurs français

KwdFr :
- Antinéoplasiques (composition chimique), Antinéoplasiques (pharmacologie), Antinéoplasiques (synthèse chimique), Apoptose (effets des médicaments et des substances chimiques), Humains (MeSH), Phosphorylation (effets des médicaments et des substances chimiques), Relation dose-effet des médicaments (MeSH), Relation structure-activité (MeSH), Sirolimus (analogues et dérivés), Sirolimus (composition chimique), Sirolimus (pharmacologie), Sirolimus (synthèse chimique), Sérine-thréonine kinases TOR (antagonistes et inhibiteurs), Tests de criblage d'agents antitumoraux (MeSH), Thérapie moléculaire ciblée (méthodes), Transduction du signal (effets des médicaments et des substances chimiques), Triazoles (pharmacologie), Triazoles (synthèse chimique).
MESH :
- analogues et dérivés : Sirolimus.
- antagonistes et inhibiteurs : Sérine-thréonine kinases TOR.
- composition chimique : Antinéoplasiques, Sirolimus.
- effets des médicaments et des substances chimiques : Apoptose, Phosphorylation, Transduction du signal.
- méthodes : Thérapie moléculaire ciblée.
- pharmacologie : Antinéoplasiques, Sirolimus, Triazoles.
- synthèse chimique : Antinéoplasiques, Sirolimus, Triazoles.
- Humains, Relation dose-effet des médicaments, Relation structure-activité, Tests de criblage d'agents antitumoraux.

English descriptors

KwdEn :
- Antineoplastic Agents (chemical synthesis), Antineoplastic Agents (chemistry), Antineoplastic Agents (pharmacology), Apoptosis (drug effects), Dose-Response Relationship, Drug (MeSH), Drug Screening Assays, Antitumor (MeSH), Humans (MeSH), Molecular Targeted Therapy (methods), Phosphorylation (drug effects), Signal Transduction (drug effects), Sirolimus (analogs & derivatives), Sirolimus (chemical synthesis), Sirolimus (chemistry), Sirolimus (pharmacology), Structure-Activity Relationship (MeSH), TOR Serine-Threonine Kinases (antagonists & inhibitors), Triazoles (chemical synthesis), Triazoles (pharmacology).
MESH :
- chemical , analogs & derivatives : Sirolimus.
- chemical , antagonists & inhibitors : TOR Serine-Threonine Kinases.
- chemical , chemical synthesis : Antineoplastic Agents, Sirolimus, Triazoles.
- chemical , chemistry : Antineoplastic Agents, Sirolimus.
- chemical , pharmacology : Antineoplastic Agents, Sirolimus, Triazoles.
- drug effects : Apoptosis, Phosphorylation, Signal Transduction.
- methods : Molecular Targeted Therapy.
- Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Structure-Activity Relationship.

Abstract

Rapamycin, a potent antifungal antibiotic, was approved as immunosuppressant, and lately its derivatives have been developed into mTOR targeting anticancer drugs. Structure modification was performed at the C-42 position of rapamycin, and a novel series of rapamycin triazole hybrids (4a-d, 5a-e, 8a-e, and 9a-e) was facilely synthesized via Huisgen's reaction. The anticancer activity of these compounds was evaluated against the Caski, H1299, MGC-803, and H460 human cancer cell lines. Some of the derivatives (8a-e, 9a-e) appeared to have stronger activity than that of rapamycin; however, 4a-d and 5a-e failed to show potential anticancer activity. Compound 9e with a (2,4-dichlorophenylamino)methyl moiety on the triazole ring was the most active anticancer compound, which showed IC50 values of 6.05 (Caski), 7.89 (H1299), 25.88 (MGC-803), and 8.60 μM (H460). In addition, research on the mechanism showed that 9e was able to cause cell morphological changes and to induce apoptosis in the Caski cell line. Most importantly, 9e can decrease the phosphorylation of mTOR and of its downstream key proteins, S6 and P70S6K1, indicating that 9e can effectively inhibit the mTOR signaling pathway. Thus, it may have the potential to become a new mTOR inhibitor against various cancers.

DOI: 10.1002/ardp.201500457
PubMed: 27150260

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000A58
to stream Main, to step Curation: 000A58

Le document en format XML

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<author><name sortKey="Lv, Youbing" sort="Lv, Youbing" uniqKey="Lv Y" first="Youbing" last="Lv">Youbing Lv</name>
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<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Synthesis of Rapamycin Derivatives Containing the Triazole Moiety Used as Potential mTOR-Targeted Anticancer Agents.</title>
<author><name sortKey="Xie, Lijun" sort="Xie, Lijun" uniqKey="Xie L" first="Lijun" last="Xie">Lijun Xie</name>
<affiliation wicri:level="3"><nlm:affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
<wicri:regionArea>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou</wicri:regionArea>
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<author><name sortKey="Huang, Jie" sort="Huang, Jie" uniqKey="Huang J" first="Jie" last="Huang">Jie Huang</name>
<affiliation wicri:level="3"><nlm:affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
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<author><name sortKey="Li, Kualiang" sort="Li, Kualiang" uniqKey="Li K" first="Kualiang" last="Li">Kualiang Li</name>
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<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
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<placeName><settlement type="city">Fuzhou</settlement>
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<author><name sortKey="Yang, Dan" sort="Yang, Dan" uniqKey="Yang D" first="Dan" last="Yang">Dan Yang</name>
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<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
<wicri:regionArea>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou</wicri:regionArea>
<placeName><settlement type="city">Fuzhou</settlement>
<region type="province">Fujian</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chen, Xiaqin" sort="Chen, Xiaqin" uniqKey="Chen X" first="Xiaqin" last="Chen">Xiaqin Chen</name>
<affiliation wicri:level="3"><nlm:affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
<wicri:regionArea>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou</wicri:regionArea>
<placeName><settlement type="city">Fuzhou</settlement>
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</placeName>
</affiliation>
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<author><name sortKey="Ying, Jiayin" sort="Ying, Jiayin" uniqKey="Ying J" first="Jiayin" last="Ying">Jiayin Ying</name>
<affiliation wicri:level="3"><nlm:affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
<wicri:regionArea>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou</wicri:regionArea>
<placeName><settlement type="city">Fuzhou</settlement>
<region type="province">Fujian</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pan, Fusheng" sort="Pan, Fusheng" uniqKey="Pan F" first="Fusheng" last="Pan">Fusheng Pan</name>
<affiliation wicri:level="3"><nlm:affiliation>Hangzhou Huadong Medicine Group Pharmaceutical Research Institute Co. Ltd., Xihu District, Hangzhou, P. R. China.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
<wicri:regionArea>Hangzhou Huadong Medicine Group Pharmaceutical Research Institute Co. Ltd., Xihu District, Hangzhou</wicri:regionArea>
<placeName><settlement type="city">Hangzhou</settlement>
<region type="province">Zhejiang</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lv, Youbing" sort="Lv, Youbing" uniqKey="Lv Y" first="Youbing" last="Lv">Youbing Lv</name>
<affiliation wicri:level="3"><nlm:affiliation>Hangzhou Huadong Medicine Group Pharmaceutical Research Institute Co. Ltd., Xihu District, Hangzhou, P. R. China.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
<wicri:regionArea>Hangzhou Huadong Medicine Group Pharmaceutical Research Institute Co. Ltd., Xihu District, Hangzhou</wicri:regionArea>
<placeName><settlement type="city">Hangzhou</settlement>
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</placeName>
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<author><name sortKey="Cheng, Yuanrong" sort="Cheng, Yuanrong" uniqKey="Cheng Y" first="Yuanrong" last="Cheng">Yuanrong Cheng</name>
<affiliation wicri:level="3"><nlm:affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
<wicri:regionArea>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou</wicri:regionArea>
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<term>Antineoplastic Agents (chemistry)</term>
<term>Antineoplastic Agents (pharmacology)</term>
<term>Apoptosis (drug effects)</term>
<term>Dose-Response Relationship, Drug (MeSH)</term>
<term>Drug Screening Assays, Antitumor (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Molecular Targeted Therapy (methods)</term>
<term>Phosphorylation (drug effects)</term>
<term>Signal Transduction (drug effects)</term>
<term>Sirolimus (analogs & derivatives)</term>
<term>Sirolimus (chemical synthesis)</term>
<term>Sirolimus (chemistry)</term>
<term>Sirolimus (pharmacology)</term>
<term>Structure-Activity Relationship (MeSH)</term>
<term>TOR Serine-Threonine Kinases (antagonists & inhibitors)</term>
<term>Triazoles (chemical synthesis)</term>
<term>Triazoles (pharmacology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Antinéoplasiques (composition chimique)</term>
<term>Antinéoplasiques (pharmacologie)</term>
<term>Antinéoplasiques (synthèse chimique)</term>
<term>Apoptose (effets des médicaments et des substances chimiques)</term>
<term>Humains (MeSH)</term>
<term>Phosphorylation (effets des médicaments et des substances chimiques)</term>
<term>Relation dose-effet des médicaments (MeSH)</term>
<term>Relation structure-activité (MeSH)</term>
<term>Sirolimus (analogues et dérivés)</term>
<term>Sirolimus (composition chimique)</term>
<term>Sirolimus (pharmacologie)</term>
<term>Sirolimus (synthèse chimique)</term>
<term>Sérine-thréonine kinases TOR (antagonistes et inhibiteurs)</term>
<term>Tests de criblage d'agents antitumoraux (MeSH)</term>
<term>Thérapie moléculaire ciblée (méthodes)</term>
<term>Transduction du signal (effets des médicaments et des substances chimiques)</term>
<term>Triazoles (pharmacologie)</term>
<term>Triazoles (synthèse chimique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Antineoplastic Agents</term>
<term>Sirolimus</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antineoplastic Agents</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Agents</term>
<term>Sirolimus</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Antinéoplasiques</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term>
<term>Phosphorylation</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Apoptose</term>
<term>Phosphorylation</term>
<term>Transduction du signal</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Molecular Targeted Therapy</term>
</keywords>
<keywords scheme="MESH" qualifier="méthodes" xml:lang="fr"><term>Thérapie moléculaire ciblée</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antinéoplasiques</term>
<term>Sirolimus</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Antinéoplasiques</term>
<term>Sirolimus</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Dose-Response Relationship, Drug</term>
<term>Drug Screening Assays, Antitumor</term>
<term>Humans</term>
<term>Structure-Activity Relationship</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Humains</term>
<term>Relation dose-effet des médicaments</term>
<term>Relation structure-activité</term>
<term>Tests de criblage d'agents antitumoraux</term>
</keywords>
</textClass>
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<front><div type="abstract" xml:lang="en">Rapamycin, a potent antifungal antibiotic, was approved as immunosuppressant, and lately its derivatives have been developed into mTOR targeting anticancer drugs. Structure modification was performed at the C-42 position of rapamycin, and a novel series of rapamycin triazole hybrids (4a-d, 5a-e, 8a-e, and 9a-e) was facilely synthesized via Huisgen's reaction. The anticancer activity of these compounds was evaluated against the Caski, H1299, MGC-803, and H460 human cancer cell lines. Some of the derivatives (8a-e, 9a-e) appeared to have stronger activity than that of rapamycin; however, 4a-d and 5a-e failed to show potential anticancer activity. Compound 9e with a (2,4-dichlorophenylamino)methyl moiety on the triazole ring was the most active anticancer compound, which showed IC50 values of 6.05 (Caski), 7.89 (H1299), 25.88 (MGC-803), and 8.60 μM (H460). In addition, research on the mechanism showed that 9e was able to cause cell morphological changes and to induce apoptosis in the Caski cell line. Most importantly, 9e can decrease the phosphorylation of mTOR and of its downstream key proteins, S6 and P70S6K1, indicating that 9e can effectively inhibit the mTOR signaling pathway. Thus, it may have the potential to become a new mTOR inhibitor against various cancers. </div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27150260</PMID>
<DateCompleted><Year>2017</Year>
<Month>03</Month>
<Day>21</Day>
</DateCompleted>
<DateRevised><Year>2017</Year>
<Month>03</Month>
<Day>21</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1521-4184</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>349</Volume>
<Issue>6</Issue>
<PubDate><Year>2016</Year>
<Month>Jun</Month>
</PubDate>
</JournalIssue>
<Title>Archiv der Pharmazie</Title>
<ISOAbbreviation>Arch Pharm (Weinheim)</ISOAbbreviation>
</Journal>
<ArticleTitle>Synthesis of Rapamycin Derivatives Containing the Triazole Moiety Used as Potential mTOR-Targeted Anticancer Agents.</ArticleTitle>
<Pagination><MedlinePgn>428-41</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1002/ardp.201500457</ELocationID>
<Abstract><AbstractText>Rapamycin, a potent antifungal antibiotic, was approved as immunosuppressant, and lately its derivatives have been developed into mTOR targeting anticancer drugs. Structure modification was performed at the C-42 position of rapamycin, and a novel series of rapamycin triazole hybrids (4a-d, 5a-e, 8a-e, and 9a-e) was facilely synthesized via Huisgen's reaction. The anticancer activity of these compounds was evaluated against the Caski, H1299, MGC-803, and H460 human cancer cell lines. Some of the derivatives (8a-e, 9a-e) appeared to have stronger activity than that of rapamycin; however, 4a-d and 5a-e failed to show potential anticancer activity. Compound 9e with a (2,4-dichlorophenylamino)methyl moiety on the triazole ring was the most active anticancer compound, which showed IC50 values of 6.05 (Caski), 7.89 (H1299), 25.88 (MGC-803), and 8.60 μM (H460). In addition, research on the mechanism showed that 9e was able to cause cell morphological changes and to induce apoptosis in the Caski cell line. Most importantly, 9e can decrease the phosphorylation of mTOR and of its downstream key proteins, S6 and P70S6K1, indicating that 9e can effectively inhibit the mTOR signaling pathway. Thus, it may have the potential to become a new mTOR inhibitor against various cancers. </AbstractText>
<CopyrightInformation>© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Xie</LastName>
<ForeName>Lijun</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Huang</LastName>
<ForeName>Jie</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chen</LastName>
<ForeName>Xiaoming</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yu</LastName>
<ForeName>Hui</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Kualiang</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yang</LastName>
<ForeName>Dan</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chen</LastName>
<ForeName>Xiaqin</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ying</LastName>
<ForeName>Jiayin</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pan</LastName>
<ForeName>Fusheng</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Hangzhou Huadong Medicine Group Pharmaceutical Research Institute Co. Ltd., Xihu District, Hangzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lv</LastName>
<ForeName>Youbing</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Hangzhou Huadong Medicine Group Pharmaceutical Research Institute Co. Ltd., Xihu District, Hangzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cheng</LastName>
<ForeName>Yuanrong</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Changshang District, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2016</Year>
<Month>05</Month>
<Day>06</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>Germany</Country>
<MedlineTA>Arch Pharm (Weinheim)</MedlineTA>
<NlmUniqueID>0330167</NlmUniqueID>
<ISSNLinking>0365-6233</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000970">Antineoplastic Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014230">Triazoles</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="C546842">MTOR protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>W36ZG6FT64</RegistryNumber>
<NameOfSubstance UI="D020123">Sirolimus</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000970" MajorTopicYN="N">Antineoplastic Agents</DescriptorName>
<QualifierName UI="Q000138" MajorTopicYN="Y">chemical synthesis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017209" MajorTopicYN="N">Apoptosis</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004354" MajorTopicYN="N">Drug Screening Assays, Antitumor</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058990" MajorTopicYN="N">Molecular Targeted Therapy</DescriptorName>
<QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D010766" MajorTopicYN="N">Phosphorylation</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D020123" MajorTopicYN="N">Sirolimus</DescriptorName>
<QualifierName UI="Q000031" MajorTopicYN="Y">analogs & derivatives</QualifierName>
<QualifierName UI="Q000138" MajorTopicYN="N">chemical synthesis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013329" MajorTopicYN="N">Structure-Activity Relationship</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014230" MajorTopicYN="N">Triazoles</DescriptorName>
<QualifierName UI="Q000138" MajorTopicYN="Y">chemical synthesis</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Anticancer activity</Keyword>
<Keyword MajorTopicYN="N">Hybrid approach</Keyword>
<Keyword MajorTopicYN="N">Rapamycin</Keyword>
<Keyword MajorTopicYN="N">Triazole</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year>
<Month>12</Month>
<Day>21</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2016</Year>
<Month>04</Month>
<Day>06</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2016</Year>
<Month>04</Month>
<Day>11</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2016</Year>
<Month>5</Month>
<Day>7</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2016</Year>
<Month>5</Month>
<Day>7</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2017</Year>
<Month>3</Month>
<Day>23</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">27150260</ArticleId>
<ArticleId IdType="doi">10.1002/ardp.201500457</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>République populaire de Chine</li>
</country>
<region><li>Fujian</li>
<li>Zhejiang</li>
</region>
<settlement><li>Fuzhou</li>
<li>Hangzhou</li>
</settlement>
</list>
<tree><country name="République populaire de Chine"><region name="Fujian"><name sortKey="Xie, Lijun" sort="Xie, Lijun" uniqKey="Xie L" first="Lijun" last="Xie">Lijun Xie</name>
</region>
<name sortKey="Chen, Xiaoming" sort="Chen, Xiaoming" uniqKey="Chen X" first="Xiaoming" last="Chen">Xiaoming Chen</name>
<name sortKey="Chen, Xiaqin" sort="Chen, Xiaqin" uniqKey="Chen X" first="Xiaqin" last="Chen">Xiaqin Chen</name>
<name sortKey="Cheng, Yuanrong" sort="Cheng, Yuanrong" uniqKey="Cheng Y" first="Yuanrong" last="Cheng">Yuanrong Cheng</name>
<name sortKey="Huang, Jie" sort="Huang, Jie" uniqKey="Huang J" first="Jie" last="Huang">Jie Huang</name>
<name sortKey="Li, Kualiang" sort="Li, Kualiang" uniqKey="Li K" first="Kualiang" last="Li">Kualiang Li</name>
<name sortKey="Lv, Youbing" sort="Lv, Youbing" uniqKey="Lv Y" first="Youbing" last="Lv">Youbing Lv</name>
<name sortKey="Pan, Fusheng" sort="Pan, Fusheng" uniqKey="Pan F" first="Fusheng" last="Pan">Fusheng Pan</name>
<name sortKey="Yang, Dan" sort="Yang, Dan" uniqKey="Yang D" first="Dan" last="Yang">Dan Yang</name>
<name sortKey="Ying, Jiayin" sort="Ying, Jiayin" uniqKey="Ying J" first="Jiayin" last="Ying">Jiayin Ying</name>
<name sortKey="Yu, Hui" sort="Yu, Hui" uniqKey="Yu H" first="Hui" last="Yu">Hui Yu</name>
</country>
</tree>
</affiliations>
</record>

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	Serveur d'exploration sur la rapamycine et les champignons
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Synthesis of Rapamycin Derivatives Containing the Triazole Moiety Used as Potential mTOR-Targeted Anticancer Agents.

Synthesis of Rapamycin Derivatives Containing the Triazole Moiety Used as Potential mTOR-Targeted Anticancer Agents.

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