与myc结合亲和力高的已上市药物

MYC有所谓不可成药性，还没有专门的靶向药上市。
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目前针对myc实际可行的治疗策略是根据患者除myc突变扩增外的其他突变，抑制其他靶点，如mtor、hsp90等，实现合成致死或蛋白降解。自救群里部分myc扩增的乳腺癌患者用了mtor抑制剂，确有疗效。
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针对治疗myc还有一种办法是通过计算机虚拟筛选等办法，在已上市药物里找与myc结合亲和力高的药物。
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% ?8 Y) B9 M2 t6 {: X* [《In Silico, In Vitro, and In Vivo Investigations on Adapalene as Repurposed Third Generation Retinoid against Multiple Myeloma and Leukemia》这篇论文，通过Virtual Screening、Molecular Docking Analyses and Microscale Thermophoresis的办法，从FDA已经批准上市的1578种药物里，筛选出一些与MYC结合亲和力高的药物；其中一些药物与MYC的结合亲和力超过常用的c-MYC 抑制剂试剂 10058-F4 和 10074-G5(LBEs of −4.92 kcal/mol and −6.24 kcal/mol)。

下面是结合亲和力比较强的一些药物：



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3 B  @% i% p& z/ \- @% M其他一些研究的结论与这篇论文的结论是相印证的，试举几例如下：
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/ {6 z% V5 n- l/ B& X6 z1、《Targeting Oncogenic Super Enhancers in MYC-Dependent AML Using a Small Molecule Activator of NR4A Nuclear Receptors》
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  E( W/ R. G9 @“MYC was identified as the most statistically repressed gene by DHE”

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$ @* g4 c" ~- W1 V2、《Drug repurposing and prediction of multiple interaction types via graph embedding》
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“Two FDA approved drugs, Dihydroergotamine (CHEMBL1732) and Indinavir Sulfate (CHEMBL1735), which are predicted by the DT2Vec+, might be able to target MYC and decrease its expression. ”

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: {) n: C7 |. r7 m. z( l3、《Involvement of MCL1, c-myc, and cyclin D2 protein degradation in ponatinib-induced cytotoxicity against T315I(+) Ph+leukemia cells》
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$ B4 P6 l" n$ o; ]4 m“PNT induced apoptosis (increased sub G1 cells, and cleaved caspase3 and PARP), and suppressed protein expression of MCL1, cyclin D2 and c-myc, which were reversed by a proteasome inhibitor, MG132, suggesting enhanced proteasomal degradation by PNT. ”


4、《 Synergistic effect of eribulin and CDK inhibition for the treatment of triple negative breast cancer》
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Additionally, treatment with eribulin resulted in a decrease in c-myc expression and a trend
3 _9 M+ h! O/ F* qtoward an increase in cdki p15。
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5、《Atovaquone: an antiprotozoal drug suppresses primary and resistant breast tumor growth by inhibiting HER2/β-catenin signaling》
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# A* m! `1 E5 Y) p: g/ H“We also observed a decrease in c-Myc expression in the tumors of atovaquone-treated mice”