PittsburghV1, Main, Exploration, bibRecord, 000F98

Targeting of the MYCN Protein with Small Molecule c-MYC Inhibitors

Identifieur interne : 000F98 ( Main/Exploration ); précédent : 000F97; suivant : 000F99

Targeting of the MYCN Protein with Small Molecule c-MYC Inhibitors

Auteurs : Inga Müller [Suède] ; Karin Larsson [Suède] ; Anna Frenzel [Suède] ; Ganna Oliynyk [Suède] ; Hanna Zirath [Suède] ; Edward V. Prochownik [États-Unis] ; Nicholas J. Westwood [Royaume-Uni] ; Marie Arsenian Henriksson [Suède]

Source :

PLoS ONE [ 1932-6203 ] ; 2014.

RBID : PMC:4032254

Descripteurs français

English descriptors

KwdEn :
- Amino Acid Sequence, Apoptosis (drug effects), Basic-Leucine Zipper Transcription Factors (metabolism), Cell Differentiation (drug effects), Cell Line, Tumor, Cell Proliferation (drug effects), Humans, Lipid Metabolism (drug effects), Molecular Sequence Data, N-Myc Proto-Oncogene Protein, Neuroblastoma (pathology), Nuclear Proteins (chemistry), Nuclear Proteins (metabolism), Oncogene Proteins (chemistry), Oncogene Proteins (metabolism), Oxadiazoles (pharmacology), Protein Folding (drug effects), Protein Structure, Tertiary, Proteolysis (drug effects), Proto-Oncogene Proteins c-myc (antagonists & inhibitors), Proto-Oncogene Proteins c-myc (chemistry), Proto-Oncogene Proteins c-myc (metabolism), Small Molecule Libraries (metabolism), Small Molecule Libraries (pharmacology).
MESH :
- chemical , antagonists & inhibitors : Proto-Oncogene Proteins c-myc.
- chemical , chemistry : Nuclear Proteins, Oncogene Proteins, Proto-Oncogene Proteins c-myc.
- chemical , metabolism : Basic-Leucine Zipper Transcription Factors, Nuclear Proteins, Oncogene Proteins, Proto-Oncogene Proteins c-myc, Small Molecule Libraries.
- drug effects : Apoptosis, Cell Differentiation, Cell Proliferation, Lipid Metabolism, Protein Folding, Proteolysis.
- pathology : Neuroblastoma.
- chemical , pharmacology : Oxadiazoles, Small Molecule Libraries.
- Amino Acid Sequence, Cell Line, Tumor, Humans, Molecular Sequence Data, N-Myc Proto-Oncogene Protein, Protein Structure, Tertiary.

Abstract

Members of the MYC family are the most frequently deregulated oncogenes in human cancer and are often correlated with aggressive disease and/or poorly differentiated tumors. Since patients with MYCN-amplified neuroblastoma have a poor prognosis, targeting MYCN using small molecule inhibitors could represent a promising therapeutic approach. We have previously demonstrated that the small molecule 10058-F4, known to bind to the c-MYC bHLHZip dimerization domain and inhibiting the c-MYC/MAX interaction, also interferes with the MYCN/MAX dimerization in vitro and imparts anti-tumorigenic effects in neuroblastoma tumor models with MYCN overexpression. Our previous work also revealed that MYCN-inhibition leads to mitochondrial dysfunction resulting in accumulation of lipid droplets in neuroblastoma cells. To expand our understanding of how small molecules interfere with MYCN, we have now analyzed the direct binding of 10058-F4, as well as three of its analogs; #474, #764 and 10058-F4(7RH), one metabolite C-m/z 232, and a structurally unrelated c-MYC inhibitor 10074-G5, to the bHLHZip domain of MYCN. We also assessed their ability to induce apoptosis, neurite outgrowth and lipid accumulation in neuroblastoma cells. Interestingly, all c-MYC binding molecules tested also bind MYCN as assayed by surface plasmon resonance. Using a proximity ligation assay, we found reduced interaction between MYCN and MAX after treatment with all molecules except for the 10058-F4 metabolite C-m/z 232 and the non-binder 10058-F4(7RH). Importantly, 10074-G5 and 10058-F4 were the most efficient in inducing neuronal differentiation and lipid accumulation in MYCN-amplified neuroblastoma cells. Together our data demonstrate MYCN-binding properties for a selection of small molecules, and provide functional information that could be of importance for future development of targeted therapies against MYCN-amplified neuroblastoma.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032254

DOI: 10.1371/journal.pone.0097285
PubMed: 24859015
PubMed Central: 4032254

Affiliations:

Le document en format XML

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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Apoptosis (drug effects)</term>
<term>Basic-Leucine Zipper Transcription Factors (metabolism)</term>
<term>Cell Differentiation (drug effects)</term>
<term>Cell Line, Tumor</term>
<term>Cell Proliferation (drug effects)</term>
<term>Humans</term>
<term>Lipid Metabolism (drug effects)</term>
<term>Molecular Sequence Data</term>
<term>N-Myc Proto-Oncogene Protein</term>
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<term>Bibliothèques de petites molécules (pharmacologie)</term>
<term>Différenciation cellulaire ()</term>
<term>Données de séquences moléculaires</term>
<term>Facteurs de transcription à motif basique et à glissière à leucines (métabolisme)</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
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<term>Neuroblastome (anatomopathologie)</term>
<term>Oxadiazoles (pharmacologie)</term>
<term>Pliage des protéines ()</term>
<term>Prolifération cellulaire ()</term>
<term>Protéine du proto-oncogène N-Myc</term>
<term>Protéines nucléaires ()</term>
<term>Protéines nucléaires (métabolisme)</term>
<term>Protéines oncogènes ()</term>
<term>Protéines oncogènes (métabolisme)</term>
<term>Protéines proto-oncogènes c-myc ()</term>
<term>Protéines proto-oncogènes c-myc (antagonistes et inhibiteurs)</term>
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<term>Séquence d'acides aminés</term>
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<term>Proto-Oncogene Proteins c-myc</term>
<term>Small Molecule Libraries</term>
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<term>Lipid Metabolism</term>
<term>Protein Folding</term>
<term>Proteolysis</term>
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<term>Facteurs de transcription à motif basique et à glissière à leucines</term>
<term>Protéines nucléaires</term>
<term>Protéines oncogènes</term>
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<term>Oxadiazoles</term>
</keywords>
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<term>Small Molecule Libraries</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Cell Line, Tumor</term>
<term>Humans</term>
<term>Molecular Sequence Data</term>
<term>N-Myc Proto-Oncogene Protein</term>
<term>Protein Structure, Tertiary</term>
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<term>Différenciation cellulaire</term>
<term>Données de séquences moléculaires</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
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<term>Protéines oncogènes</term>
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<front><div type="abstract" xml:lang="en"><p>Members of the <italic>MYC</italic>
 family are the most frequently deregulated oncogenes in human cancer and are often correlated with aggressive disease and/or poorly differentiated tumors. Since patients with <italic>MYCN</italic>
-amplified neuroblastoma have a poor prognosis, targeting MYCN using small molecule inhibitors could represent a promising therapeutic approach. We have previously demonstrated that the small molecule 10058-F4, known to bind to the c-MYC bHLHZip dimerization domain and inhibiting the c-MYC/MAX interaction, also interferes with the MYCN/MAX dimerization <italic>in vitro</italic>
 and imparts anti-tumorigenic effects in neuroblastoma tumor models with <italic>MYCN</italic>
 overexpression. Our previous work also revealed that MYCN-inhibition leads to mitochondrial dysfunction resulting in accumulation of lipid droplets in neuroblastoma cells. To expand our understanding of how small molecules interfere with MYCN, we have now analyzed the direct binding of 10058-F4, as well as three of its analogs; #474, #764 and 10058-F4(7RH), one metabolite C-<italic>m/z</italic>
 232, and a structurally unrelated c-MYC inhibitor 10074-G5, to the bHLHZip domain of MYCN. We also assessed their ability to induce apoptosis, neurite outgrowth and lipid accumulation in neuroblastoma cells. Interestingly, all c-MYC binding molecules tested also bind MYCN as assayed by surface plasmon resonance. Using a proximity ligation assay, we found reduced interaction between MYCN and MAX after treatment with all molecules except for the 10058-F4 metabolite C-<italic>m/z</italic>
 232 and the non-binder 10058-F4(7RH). Importantly, 10074-G5 and 10058-F4 were the most efficient in inducing neuronal differentiation and lipid accumulation in <italic>MYCN</italic>
-amplified neuroblastoma cells. Together our data demonstrate MYCN-binding properties for a selection of small molecules, and provide functional information that could be of importance for future development of targeted therapies against <italic>MYCN</italic>
-amplified neuroblastoma.</p>
</div>
</front>
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<biblStruct><analytic><author><name sortKey="Malynn, Ba" uniqKey="Malynn B">BA Malynn</name>
</author>
<author><name sortKey="De Alboran, Im" uniqKey="De Alboran I">IM de Alboran</name>
</author>
<author><name sortKey="O Hagan, Rc" uniqKey="O Hagan R">RC O'Hagan</name>
</author>
<author><name sortKey="Bronson, R" uniqKey="Bronson R">R Bronson</name>
</author>
<author><name sortKey="Davidson, L" uniqKey="Davidson L">L Davidson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Downs, Km" uniqKey="Downs K">KM Downs</name>
</author>
<author><name sortKey="Martin, Gr" uniqKey="Martin G">GR Martin</name>
</author>
<author><name sortKey="Bishop, Jm" uniqKey="Bishop J">JM Bishop</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zimmerman, Ka" uniqKey="Zimmerman K">KA Zimmerman</name>
</author>
<author><name sortKey="Yancopoulos, Gd" uniqKey="Yancopoulos G">GD Yancopoulos</name>
</author>
<author><name sortKey="Collum, Rg" uniqKey="Collum R">RG Collum</name>
</author>
<author><name sortKey="Smith, Rk" uniqKey="Smith R">RK Smith</name>
</author>
<author><name sortKey="Kohl, Ne" uniqKey="Kohl N">NE Kohl</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hirvonen, H" uniqKey="Hirvonen H">H Hirvonen</name>
</author>
<author><name sortKey="Makela, Tp" uniqKey="Makela T">TP Makela</name>
</author>
<author><name sortKey="Sandberg, M" uniqKey="Sandberg M">M Sandberg</name>
</author>
<author><name sortKey="Kalimo, H" uniqKey="Kalimo H">H Kalimo</name>
</author>
<author><name sortKey="Vuorio, E" uniqKey="Vuorio E">E Vuorio</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mugrauer, G" uniqKey="Mugrauer G">G Mugrauer</name>
</author>
<author><name sortKey="Alt, Fw" uniqKey="Alt F">FW Alt</name>
</author>
<author><name sortKey="Ekblom, P" uniqKey="Ekblom P">P Ekblom</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stanton, Br" uniqKey="Stanton B">BR Stanton</name>
</author>
<author><name sortKey="Parada, Lf" uniqKey="Parada L">LF Parada</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Albihn, A" uniqKey="Albihn A">A Albihn</name>
</author>
<author><name sortKey="Johnsen, Ji" uniqKey="Johnsen J">JI Johnsen</name>
</author>
<author><name sortKey="Henriksson, Ma" uniqKey="Henriksson M">MA Henriksson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Brodeur, Gm" uniqKey="Brodeur G">GM Brodeur</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Maris, Jm" uniqKey="Maris J">JM Maris</name>
</author>
<author><name sortKey="Hogarty, Md" uniqKey="Hogarty M">MD Hogarty</name>
</author>
<author><name sortKey="Bagatell, R" uniqKey="Bagatell R">R Bagatell</name>
</author>
<author><name sortKey="Cohn, Sl" uniqKey="Cohn S">SL Cohn</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Larsson, Lg" uniqKey="Larsson L">LG Larsson</name>
</author>
<author><name sortKey="Henriksson, Ma" uniqKey="Henriksson M">MA Henriksson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Prochownik, Ev" uniqKey="Prochownik E">EV Prochownik</name>
</author>
<author><name sortKey="Vogt, Pk" uniqKey="Vogt P">PK Vogt</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Felsher, Dw" uniqKey="Felsher D">DW Felsher</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Felsher, Dw" uniqKey="Felsher D">DW Felsher</name>
</author>
<author><name sortKey="Bishop, Jm" uniqKey="Bishop J">JM Bishop</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jain, M" uniqKey="Jain M">M Jain</name>
</author>
<author><name sortKey="Arvanitis, C" uniqKey="Arvanitis C">C Arvanitis</name>
</author>
<author><name sortKey="Chu, K" uniqKey="Chu K">K Chu</name>
</author>
<author><name sortKey="Dewey, W" uniqKey="Dewey W">W Dewey</name>
</author>
<author><name sortKey="Leonhardt, E" uniqKey="Leonhardt E">E Leonhardt</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pelengaris, S" uniqKey="Pelengaris S">S Pelengaris</name>
</author>
<author><name sortKey="Khan, M" uniqKey="Khan M">M Khan</name>
</author>
<author><name sortKey="Evan, Gi" uniqKey="Evan G">GI Evan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pelengaris, S" uniqKey="Pelengaris S">S Pelengaris</name>
</author>
<author><name sortKey="Littlewood, T" uniqKey="Littlewood T">T Littlewood</name>
</author>
<author><name sortKey="Khan, M" uniqKey="Khan M">M Khan</name>
</author>
<author><name sortKey="Elia, G" uniqKey="Elia G">G Elia</name>
</author>
<author><name sortKey="Evan, G" uniqKey="Evan G">G Evan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shachaf, Cm" uniqKey="Shachaf C">CM Shachaf</name>
</author>
<author><name sortKey="Felsher, Dw" uniqKey="Felsher D">DW Felsher</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shachaf, Cm" uniqKey="Shachaf C">CM Shachaf</name>
</author>
<author><name sortKey="Kopelman, Am" uniqKey="Kopelman A">AM Kopelman</name>
</author>
<author><name sortKey="Arvanitis, C" uniqKey="Arvanitis C">C Arvanitis</name>
</author>
<author><name sortKey="Karlsson, A" uniqKey="Karlsson A">A Karlsson</name>
</author>
<author><name sortKey="Beer, S" uniqKey="Beer S">S Beer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Soucek, L" uniqKey="Soucek L">L Soucek</name>
</author>
<author><name sortKey="Evan, Gi" uniqKey="Evan G">GI Evan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Soucek, L" uniqKey="Soucek L">L Soucek</name>
</author>
<author><name sortKey="Whitfield, J" uniqKey="Whitfield J">J Whitfield</name>
</author>
<author><name sortKey="Martins, Cp" uniqKey="Martins C">CP Martins</name>
</author>
<author><name sortKey="Finch, Aj" uniqKey="Finch A">AJ Finch</name>
</author>
<author><name sortKey="Murphy, Dj" uniqKey="Murphy D">DJ Murphy</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dang, Cv" uniqKey="Dang C">CV Dang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Loke, Sl" uniqKey="Loke S">SL Loke</name>
</author>
<author><name sortKey="Stein, C" uniqKey="Stein C">C Stein</name>
</author>
<author><name sortKey="Zhang, X" uniqKey="Zhang X">X Zhang</name>
</author>
<author><name sortKey="Avigan, M" uniqKey="Avigan M">M Avigan</name>
</author>
<author><name sortKey="Cohen, J" uniqKey="Cohen J">J Cohen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Siddiqui Jain, A" uniqKey="Siddiqui Jain A">A Siddiqui-Jain</name>
</author>
<author><name sortKey="Grand, Cl" uniqKey="Grand C">CL Grand</name>
</author>
<author><name sortKey="Bearss, Dj" uniqKey="Bearss D">DJ Bearss</name>
</author>
<author><name sortKey="Hurley, Lh" uniqKey="Hurley L">LH Hurley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Berg, T" uniqKey="Berg T">T Berg</name>
</author>
<author><name sortKey="Cohen, Sb" uniqKey="Cohen S">SB Cohen</name>
</author>
<author><name sortKey="Desharnais, J" uniqKey="Desharnais J">J Desharnais</name>
</author>
<author><name sortKey="Sonderegger, C" uniqKey="Sonderegger C">C Sonderegger</name>
</author>
<author><name sortKey="Maslyar, Dj" uniqKey="Maslyar D">DJ Maslyar</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yin, X" uniqKey="Yin X">X Yin</name>
</author>
<author><name sortKey="Giap, C" uniqKey="Giap C">C Giap</name>
</author>
<author><name sortKey="Lazo, Js" uniqKey="Lazo J">JS Lazo</name>
</author>
<author><name sortKey="Prochownik, Ev" uniqKey="Prochownik E">EV Prochownik</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Follis, Av" uniqKey="Follis A">AV Follis</name>
</author>
<author><name sortKey="Hammoudeh, Di" uniqKey="Hammoudeh D">DI Hammoudeh</name>
</author>
<author><name sortKey="Daab, At" uniqKey="Daab A">AT Daab</name>
</author>
<author><name sortKey="Metallo, Sj" uniqKey="Metallo S">SJ Metallo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Follis, Av" uniqKey="Follis A">AV Follis</name>
</author>
<author><name sortKey="Hammoudeh, Di" uniqKey="Hammoudeh D">DI Hammoudeh</name>
</author>
<author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name>
</author>
<author><name sortKey="Prochownik, Ev" uniqKey="Prochownik E">EV Prochownik</name>
</author>
<author><name sortKey="Metallo, Sj" uniqKey="Metallo S">SJ Metallo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Harvey, Sr" uniqKey="Harvey S">SR Harvey</name>
</author>
<author><name sortKey="Porrini, M" uniqKey="Porrini M">M Porrini</name>
</author>
<author><name sortKey="Stachl, C" uniqKey="Stachl C">C Stachl</name>
</author>
<author><name sortKey="Macmillan, D" uniqKey="Macmillan D">D MacMillan</name>
</author>
<author><name sortKey="Zinzalla, G" uniqKey="Zinzalla G">G Zinzalla</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Michel, J" uniqKey="Michel J">J Michel</name>
</author>
<author><name sortKey="Cuchillo, R" uniqKey="Cuchillo R">R Cuchillo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Huang, Mj" uniqKey="Huang M">MJ Huang</name>
</author>
<author><name sortKey="Cheng, Yc" uniqKey="Cheng Y">YC Cheng</name>
</author>
<author><name sortKey="Liu, Cr" uniqKey="Liu C">CR Liu</name>
</author>
<author><name sortKey="Lin, S" uniqKey="Lin S">S Lin</name>
</author>
<author><name sortKey="Liu, He" uniqKey="Liu H">HE Liu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lin, Cp" uniqKey="Lin C">CP Lin</name>
</author>
<author><name sortKey="Liu, Jd" uniqKey="Liu J">JD Liu</name>
</author>
<author><name sortKey="Chow, Jm" uniqKey="Chow J">JM Chow</name>
</author>
<author><name sortKey="Liu, Cr" uniqKey="Liu C">CR Liu</name>
</author>
<author><name sortKey="Liu, He" uniqKey="Liu H">HE Liu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rahl, Pb" uniqKey="Rahl P">PB Rahl</name>
</author>
<author><name sortKey="Lin, Cy" uniqKey="Lin C">CY Lin</name>
</author>
<author><name sortKey="Seila, Ac" uniqKey="Seila A">AC Seila</name>
</author>
<author><name sortKey="Flynn, Ra" uniqKey="Flynn R">RA Flynn</name>
</author>
<author><name sortKey="Mccuine, S" uniqKey="Mccuine S">S McCuine</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Guo, J" uniqKey="Guo J">J Guo</name>
</author>
<author><name sortKey="Parise, Ra" uniqKey="Parise R">RA Parise</name>
</author>
<author><name sortKey="Joseph, E" uniqKey="Joseph E">E Joseph</name>
</author>
<author><name sortKey="Egorin, Mj" uniqKey="Egorin M">MJ Egorin</name>
</author>
<author><name sortKey="Lazo, Js" uniqKey="Lazo J">JS Lazo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Clausen, Dm" uniqKey="Clausen D">DM Clausen</name>
</author>
<author><name sortKey="Guo, J" uniqKey="Guo J">J Guo</name>
</author>
<author><name sortKey="Parise, Ra" uniqKey="Parise R">RA Parise</name>
</author>
<author><name sortKey="Beumer, Jh" uniqKey="Beumer J">JH Beumer</name>
</author>
<author><name sortKey="Egorin, Mj" uniqKey="Egorin M">MJ Egorin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hammoudeh, Di" uniqKey="Hammoudeh D">DI Hammoudeh</name>
</author>
<author><name sortKey="Follis, Av" uniqKey="Follis A">AV Follis</name>
</author>
<author><name sortKey="Prochownik, Ev" uniqKey="Prochownik E">EV Prochownik</name>
</author>
<author><name sortKey="Metallo, Sj" uniqKey="Metallo S">SJ Metallo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name>
</author>
<author><name sortKey="Hammoudeh, Di" uniqKey="Hammoudeh D">DI Hammoudeh</name>
</author>
<author><name sortKey="Follis, Av" uniqKey="Follis A">AV Follis</name>
</author>
<author><name sortKey="Reese, Be" uniqKey="Reese B">BE Reese</name>
</author>
<author><name sortKey="Lazo, Js" uniqKey="Lazo J">JS Lazo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zirath, H" uniqKey="Zirath H">H Zirath</name>
</author>
<author><name sortKey="Frenzel, A" uniqKey="Frenzel A">A Frenzel</name>
</author>
<author><name sortKey="Oliynyk, G" uniqKey="Oliynyk G">G Oliynyk</name>
</author>
<author><name sortKey="Segerstrom, L" uniqKey="Segerstrom L">L Segerstrom</name>
</author>
<author><name sortKey="Westermark, Uk" uniqKey="Westermark U">UK Westermark</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dyson, Hj" uniqKey="Dyson H">HJ Dyson</name>
</author>
<author><name sortKey="Wright, Pe" uniqKey="Wright P">PE Wright</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Andrade, Ma" uniqKey="Andrade M">MA Andrade</name>
</author>
<author><name sortKey="Chacon, P" uniqKey="Chacon P">P Chacon</name>
</author>
<author><name sortKey="Merelo, Jj" uniqKey="Merelo J">JJ Merelo</name>
</author>
<author><name sortKey="Moran, F" uniqKey="Moran F">F Moran</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sreerama, N" uniqKey="Sreerama N">N Sreerama</name>
</author>
<author><name sortKey="Venyaminov, Sy" uniqKey="Venyaminov S">SY Venyaminov</name>
</author>
<author><name sortKey="Woody, Rw" uniqKey="Woody R">RW Woody</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sreerama, N" uniqKey="Sreerama N">N Sreerama</name>
</author>
<author><name sortKey="Woody, Rw" uniqKey="Woody R">RW Woody</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Van Stokkum, Ih" uniqKey="Van Stokkum I">IH van Stokkum</name>
</author>
<author><name sortKey="Spoelder, Hj" uniqKey="Spoelder H">HJ Spoelder</name>
</author>
<author><name sortKey="Bloemendal, M" uniqKey="Bloemendal M">M Bloemendal</name>
</author>
<author><name sortKey="Van Grondelle, R" uniqKey="Van Grondelle R">R van Grondelle</name>
</author>
<author><name sortKey="Groen, Fc" uniqKey="Groen F">FC Groen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Whitmore, L" uniqKey="Whitmore L">L Whitmore</name>
</author>
<author><name sortKey="Wallace, Ba" uniqKey="Wallace B">BA Wallace</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Whitmore, L" uniqKey="Whitmore L">L Whitmore</name>
</author>
<author><name sortKey="Wallace, Ba" uniqKey="Wallace B">BA Wallace</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fieber, W" uniqKey="Fieber W">W Fieber</name>
</author>
<author><name sortKey="Schneider, Ml" uniqKey="Schneider M">ML Schneider</name>
</author>
<author><name sortKey="Matt, T" uniqKey="Matt T">T Matt</name>
</author>
<author><name sortKey="Kr Utler, B" uniqKey="Kr Utler B">B Kräutler</name>
</author>
<author><name sortKey="Konrat, R" uniqKey="Konrat R">R Konrat</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Edsjo, A" uniqKey="Edsjo A">A Edsjo</name>
</author>
<author><name sortKey="Holmquist, L" uniqKey="Holmquist L">L Holmquist</name>
</author>
<author><name sortKey="Pahlman, S" uniqKey="Pahlman S">S Pahlman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Knoepfler, Ps" uniqKey="Knoepfler P">PS Knoepfler</name>
</author>
<author><name sortKey="Cheng, Pf" uniqKey="Cheng P">PF Cheng</name>
</author>
<author><name sortKey="Eisenman, Rn" uniqKey="Eisenman R">RN Eisenman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Loven, Jz" uniqKey="Loven J">JZ Loven</name>
</author>
<author><name sortKey="Zinin, N" uniqKey="Zinin N">N Zinin</name>
</author>
<author><name sortKey="Wahlstrom, T" uniqKey="Wahlstrom T">T Wahlström</name>
</author>
<author><name sortKey="Muller, I" uniqKey="Muller I">I Müller</name>
</author>
<author><name sortKey="Brodin, P" uniqKey="Brodin P">P Brodin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yap, Jl" uniqKey="Yap J">JL Yap</name>
</author>
<author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name>
</author>
<author><name sortKey="Hu, A" uniqKey="Hu A">A Hu</name>
</author>
<author><name sortKey="Chauhan, J" uniqKey="Chauhan J">J Chauhan</name>
</author>
<author><name sortKey="Jung, Ky" uniqKey="Jung K">KY Jung</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wang, Hc" uniqKey="Wang H">HC Wang</name>
</author>
<author><name sortKey="Hu, J" uniqKey="Hu J">J Hu</name>
</author>
<author><name sortKey="Pendleton, A" uniqKey="Pendleton A">A Pendleton</name>
</author>
<author><name sortKey="Yap, K" uniqKey="Yap K">K Yap</name>
</author>
<author><name sortKey="Sabato, Jl" uniqKey="Sabato J">JL Sabato</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Albihn, A" uniqKey="Albihn A">A Albihn</name>
</author>
<author><name sortKey="Loven, J" uniqKey="Loven J">J Loven</name>
</author>
<author><name sortKey="Ohlsson, J" uniqKey="Ohlsson J">J Ohlsson</name>
</author>
<author><name sortKey="Osorio, Lm" uniqKey="Osorio L">LM Osorio</name>
</author>
<author><name sortKey="Henriksson, M" uniqKey="Henriksson M">M Henriksson</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
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</region>
</country>
<country name="Royaume-Uni"><noRegion><name sortKey="Westwood, Nicholas J" sort="Westwood, Nicholas J" uniqKey="Westwood N" first="Nicholas J." last="Westwood">Nicholas J. Westwood</name>
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</record>

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EXPLOR_STEP=$WICRI_ROOT/Wicri/Amérique/explor/PittsburghV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000F98 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000F98 | SxmlIndent | more

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{{Explor lien
   |wiki=    Wicri/Amérique
   |area=    PittsburghV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     PMC:4032254
   |texte=   Targeting of the MYCN Protein with Small Molecule c-MYC Inhibitors
}}

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HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:24859015" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a PittsburghV1

This area was generated with Dilib version V0.6.38.
Data generation: Fri Jun 18 17:37:45 2021. Site generation: Fri Jun 18 18:15:47 2021

Serveur d'exploration sur Pittsburgh

Targeting of the MYCN Protein with Small Molecule c-MYC Inhibitors

Targeting of the MYCN Protein with Small Molecule c-MYC Inhibitors

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English descriptors

Abstract

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Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

	Serveur d'exploration sur Pittsburgh
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.