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。
《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：
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：
1、《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》
“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. ”
3、《Involvement of MCL1, c-myc, and cyclin D2 protein degradation in ponatinib-induced cytotoxicity against T315I(+) Ph+leukemia cells》
“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》
Additionally, treatment with eribulin resulted in a decrease in c-myc expression and a trend
toward an increase in cdki p15。
5、《Atovaquone: an antiprotozoal drug suppresses primary and resistant breast tumor growth by inhibiting HER2/β-catenin signaling》
“We also observed a decrease in c-Myc expression in the tumors of atovaquone-treated mice”
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