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。
' Q8 J$ g" o# E* @7 ~( g
2 f5 s: ?2 h3 [+ Y% W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。

0 Z. v! O! E- O! p( R2 A; O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)。

8 Z* g0 C+ j, H1 R9 {! F下面是结合亲和力比较强的一些药物：

: y( h! b4 Y3 w
0 ?+ D' y1 w6 Z: E/ h* _
1 M; L8 O" _' x" A: d$ X7 F& s& ^
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：

* ^: K+ {; K; k$ z& f8 g) d8 l
1、《Targeting Oncogenic Super Enhancers in MYC-Dependent AML Using a Small Molecule Activator of NR4A Nuclear Receptors》
: w$ B: N) b7 X& U! P
* c! _% P& v5 ]. U“MYC was identified as the most statistically repressed gene by DHE”



3 ^/ O4 K+ R1 F1 j+ T" m2、《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. ”

5 N4 ^3 y# J( a, T9 e
3 m/ L# U' q5 H; a, S
" v7 t% X+ f0 i/ g3、《Involvement of MCL1, c-myc, and cyclin D2 protein degradation in ponatinib-induced cytotoxicity against T315I(+) Ph+leukemia cells》

5 J$ L, z' T8 W3 U“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. ”

. J' r5 n6 a/ V0 p, C2 u! q
8 B' R0 p8 `- s" Z8 s4、《 Synergistic effect of eribulin and CDK inhibition for the treatment of triple negative breast cancer》
% B/ ~* ^/ g8 ]; O0 h
9 }- T' E4 R. O2 A2 O* m Additionally, treatment with eribulin resulted in a decrease in c-myc expression and a trend
$ e7 K# _- k3 x+ X  U( z9 otoward 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”