Table 1.
Selected DIPG-specific screening hits with available inhibitors
| Screening Hit | Rank | Fold Change (log2) | Adj. P-value | Inhibitor | Targets |
|---|---|---|---|---|---|
| PPP2R1A | 6 | −1.220 | 0.012 | LB-100 | PP2A |
| PRKDC | 11 | −1.092 | 0.025 | NU7026 | DNA-PK |
| NU7441 | |||||
| HMGB2 | 17 | −0.982 | 0.058 | Inflachromene | HMGB2 |
| NOTCH4 | 24 | −0.903 | 0.027 | RO4929097 | γ-Secretase |
| CDC25B | 28 | −0.866 | 0.002 | NSC95397 | CDC25A, CDC25B |
| CDC25A | 33 | −0.843 | 0.027 | ||
| SMAD2 | 32 | −0.851 | 0.001 | LY2109761 | TGF-β receptor type I/II |
| ERCC2 | 39 | −0.813 | 0.078 | Spironolactone | XPB/ERCC3 |
| CPT1B | 41 | −0.803 | 0.053 | Etomoxir | CPT-1, PPARα |
| ERBB3 | 42 | −0.793 | 0.011 | Sapitinib | ERBB3 |
| EGF | 77 | −0.704 | 0.025 | Afatinib | ERBB2, EGFR |
| FGF2 | 94 | −0.656 | 0.072 | AZD4547 | FGFR1, FGFR2, FGFR3 |
| Dovitinib | FGFR1, FGFR3 | ||||
| PD173074 | FGFR1 | ||||
| Ponatinib | |||||
| UBE2V2 | 101 | −0.620 | 0.012 | NSC697923 | Ubc13/UBE2N-UEV1A |
| DNA repair | n/a | n/a | n/a | Gimeracil | DPYD/homologous recombination |
| YU238259 | Homology-dependent DNA repair | ||||
| SCR7 | LIG4/non-homologous end joining | ||||
| Reference drugs | |||||
| – | – | – | – | Niraparib | PARP1, PARP2 |
| – | – | – | – | Temozolomide | Alkylating DNA |
TGF-β = transforming growth factor beta; PPAR = peroxisome proliferator-activated receptor.
Additional targets of each inhibitor are specified in Supplementary Table 6.