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10.1038/s41598-018-28107-4 http://scihub22266oqcxt.onion/10.1038/s41598-018-28107-4 C6030159!6030159 !29968736     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\29968736 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Sci+Rep 2018 ; 8 (1 ): 10064 Nephropedia Template TP {{tp|p=29968736 |t=2018. A selective high affinity MYC-binding compound inhibits MYC:MAX interaction and MYC-dependent tumor cell proliferation |pdf=|usr=}}{{29968736 }} gab.com Text A selective high affinity MYC-binding compound inhibits MYC:MAX interaction and MYC-dependent tumor cell proliferation JO: Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=29968736 #FOAvip MYC is a key player in tumor development, but unfortunately no specific MYC-targeting drugs are clinically available. MYC is strictly dependent on heterodimerization with MAX for transcription activation. Aiming at targeting this interaction, we identified MYCMI-6 in a cell-based protein interaction screen for small inhibitory molecules. MYCMI-6 exhibits strong selective inhibition of MYC:MAX interaction in cells and in vitro at single-digit micromolar concentrations, as validated by split Gaussia luciferase, in situ proximity ligation, microscale thermophoresis and surface plasmon resonance (SPR) assays. Further, MYCMI-6 blocks MYC-driven transcription and binds selectively to the MYC bHLHZip domain with a K(D) of 1.6?±?0.5??M as demonstrated by SPR. MYCMI-6 inhibits tumor cell growth in a MYC-dependent manner with IC(50) concentrations as low as 0.5??M, while sparing normal cells. The response to MYCMI-6 correlates with MYC expression based on data from 60 human tumor cell lines and is abrogated by MYC depletion. Further, it inhibits MYC:MAX interaction, reduces proliferation and induces massive apoptosis in tumor tissue from a MYC-driven xenograft tumor model without severe side effects. Since MYCMI-6 does not affect MYC expression, it is a unique molecular tool to specifically target MYC:MAX pharmacologically and it has good potential for drug development. Twit Text FOAVip A selective high affinity MYC-binding compound inhibits MYC:MAX interaction and MYC-dependent tumor cell proliferation ????Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=29968736 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29968736 #FOAvip English Wikipedia <ref>{{Cite pmid|29968736 }}</ref> A selective high affinity MYC-binding compound inhibits MYC:MAX interaction and MYC-dependent tumor cell proliferation #MMPMID29968736 Castell A ; Yan Q ; Fawkner K ; Hydbring P ; Zhang F ; Verschut V ; Franco M ; Zakaria SM ; Bazzar W ; Goodwin J ; Zinzalla G ; Larsson LG Sci Rep 2018[Jul]; 8 (1 ): 10064 PMID29968736 show ga MYC is a key player in tumor development, but unfortunately no specific MYC-targeting drugs are clinically available. MYC is strictly dependent on heterodimerization with MAX for transcription activation. Aiming at targeting this interaction, we identified MYCMI-6 in a cell-based protein interaction screen for small inhibitory molecules. MYCMI-6 exhibits strong selective inhibition of MYC:MAX interaction in cells and in vitro at single-digit micromolar concentrations, as validated by split Gaussia luciferase, in situ proximity ligation, microscale thermophoresis and surface plasmon resonance (SPR) assays. Further, MYCMI-6 blocks MYC-driven transcription and binds selectively to the MYC bHLHZip domain with a K(D) of 1.6?±?0.5??M as demonstrated by SPR. MYCMI-6 inhibits tumor cell growth in a MYC-dependent manner with IC(50) concentrations as low as 0.5??M, while sparing normal cells. The response to MYCMI-6 correlates with MYC expression based on data from 60 human tumor cell lines and is abrogated by MYC depletion. Further, it inhibits MYC:MAX interaction, reduces proliferation and induces massive apoptosis in tumor tissue from a MYC-driven xenograft tumor model without severe side effects. Since MYCMI-6 does not affect MYC expression, it is a unique molecular tool to specifically target MYC:MAX pharmacologically and it has good potential for drug development. |Animals [MESH] |Apoptosis/physiology [MESH] |Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*antagonists & inhibitors/*metabolism [MESH] |COS Cells [MESH] |Cell Line, Tumor [MESH] |Cell Proliferation/drug effects [MESH] |Chlorocebus aethiops [MESH] |Diamines/*pharmacology [MESH] |Drug Screening Assays, Antitumor [MESH] |HEK293 Cells [MESH] |HeLa Cells [MESH] |High-Throughput Screening Assays/methods [MESH] |Humans [MESH] |MCF-7 Cells [MESH] |Mice [MESH] |Mice, Nude [MESH] |Protein Binding/drug effects [MESH] |Proto-Oncogene Proteins c-myc/*antagonists & inhibitors/*metabolism [MESH] |Pyridines/*pharmacology [MESH] |Small Molecule Libraries/pharmacology [MESH] |Transcriptional Activation [MESH]A selective high affinity MYC-binding compound inhibits MYC:MAX intera(epmc).pdf DeepDyve Pubget Overpricing