·Selection of small molecule compounds was based on the previously published transcriptome analysis of 8 cases of DIPG and 6 cases of normal brain tissues. New inhibitory compounds of DIPG were identified by single agent screening in DIPG primary tumor cells. The changes of target genes at mRNA and protein expression level were detected by real-time PCR and Western blotting after drug treatment. The effects of drug treatment on the proliferation and apoptosis of DIPG primary tumor cells were detected by FACS analyses after EdU and Annexin V/propidium iodide staining, respectively. The combinatory screening of small molecular compounds was performed with bromodomain and extra terminal protein (BET) inhibitor JQ1 or histone deacetylase (HDAC) inhibitor panobinostat, and the drug combination with inhibitory effect on DIPG was verified in vitro.

·Sixty-six small molecules were chosen to be applied to screening. Single agent screening identified that YM155 could significantly inhibit DIPG primary tumor cell growth, and BIRC5 (baculoviral IAP repeat containing 5; gene encoding survivin), a target gene of YM155, was significantly upregulated in DIPG tumor tissues (P=0.018). YM155 could reduce the expression of BICR5 at both mRNA and protein levels. YM155 could repress proliferation and induce apoptosis of DIPG. CX4945 and ABT-737 from the targeted small molecular library were combined with JQ1 (BET inhibitor) and panobinostat (HDAC inhibitor), respectively,which could synergistically inhibit the activity of DIPG cells in vitro.

·Novel targeted therapeutic strategies for DIPG has been identified through single drug and combination drug screening, providing basis for furthervalidation in vivo and therapeutic mechanism exploration.