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。

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。

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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9 I; R& H! L$ [《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)。
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下面是结合亲和力比较强的一些药物：

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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：


! s% n/ N7 p' S/ b/ E2 |) g' x' u1、《Targeting Oncogenic Super Enhancers in MYC-Dependent AML Using a Small Molecule Activator of NR4A Nuclear Receptors》

“MYC was identified as the most statistically repressed gene by DHE”



2、《Drug repurposing and prediction of multiple interaction types via graph embedding》

' t& j6 q* k4 P( H“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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% _' S, ^. b# a2 Z3、《Involvement of MCL1, c-myc, and cyclin D2 protein degradation in ponatinib-induced cytotoxicity against T315I(+) Ph+leukemia cells》
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3 b( a9 z& w1 Y6 c* _. J( p& W“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. ”

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  s, o) C' L+ D% N5 C( O% c4、《 Synergistic effect of eribulin and CDK inhibition for the treatment of triple negative breast cancer》

Additionally, treatment with eribulin resulted in a decrease in c-myc expression and a trend
9 U& p2 g' s, o* `toward an increase in cdki p15。


5、《Atovaquone: an antiprotozoal drug suppresses primary and resistant breast tumor growth by inhibiting HER2/β-catenin signaling》
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5 S& T4 C" R* O; m0 C6 L' P8 f4 `2 ~“We also observed a decrease in c-Myc expression in the tumors of atovaquone-treated mice”