Supplementary Materials

The PDF file includes:

  • Materials and Methods
  • Fig. S1. MIPE library annotations, correlation analysis of MIPE 5.0 screens, and additional potency distributions.
  • Fig. S2. MoA similarities defined by clustering analyses of combination assessments.
  • Fig. S3. Combination assessments of drugs in active DIPG clinical evaluations.
  • Fig. S4. DIPG cell viability after treatment with candidate combinations.
  • Fig. S5. Flow cytometry analysis of BMS-754807– and selumetinib-treated DIPG cells.
  • Fig. S6. BMS-754807 and selumetinib in vivo alone or in combination with panobinostat and assessment of the effect of panobinostat and marizomib on brain viability.
  • Fig. S7. Efficacy of panobinostat alone and with marizomib on nonpontine DMG.
  • Fig. S8. Effect of extended treatment with panobinostat and marizomib on normal and malignant cell viability.
  • Fig. S9. Transcriptional responses to panobinostat and marizomib treatment in SU-DIPGXIII cells.
  • Fig. S10. GSEA of panobinostat and marizomib treatment in SU-DIPG-XIII cells.
  • Fig. S11. Transcriptional analysis of panobinostat and marizomib treatments in SU-DIPGVI and QCTB-R059 cells.
  • Fig. S12. Effects of panobinostat and marizomib treatment on ER stress and the UPR pathway in DIPG cells.
  • Fig. S13. Down-regulated transcriptional programs in SU-DIPG-VI and QCTB-R059 cells.
  • Fig. S14. Drug-induced metabolic rewiring and collapse in DIPG.
  • Fig. S15. Lack of rescue by the ROS mitigator N-acetylcysteine from proteasome inhibition and HDAC inhibitor–induced toxicity in DIPG.
  • Fig. S16. Effects of metabolic and NAD+ perturbations on DIPG.
  • Reference (42)

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Other Supplementary Material for this manuscript includes the following:

  • Data file S1 contains tables S1 to S11.
  • Table S1 (Microsoft Excel format). Listing of all PubChem AIDs for all single-agent screening data.
  • Table S2 (Microsoft Excel format). Complete listing of agents, MoAs, clinical phase, and CAS numbers for the MIPE 5.0 library.
  • Table S3 (Microsoft Excel format). MoA distribution for all MIPE 5.0 library members.
  • Table S4 (Microsoft Excel format). Complete listing of 371 potency-selected agents.
  • Table S5 (Microsoft Excel format). Complete listing of agents in current or recently completed clinical trials for DIPG.
  • Table S6 (Microsoft Excel format). Complete listing of agents with average Z-AUC < −2.0 and predicted CNS exposure (MPO score > 4.4).
  • Table S7 (Microsoft Excel format). Complete listing of outcomes from the panobinostat “drug-versus-all” experiment in SU-DIPG-XXV.
  • Table S8 (Microsoft Excel format). Complete listing of outcomes from the marizomib drug-versus-all experiment in SU-DIPG-XXV.
  • Table S9 (Microsoft Excel format). Complete listing of outcomes from the 45-agent all-versus-all experiment in SU-DIPG-XXV.
  • Table S10 (Microsoft Excel format). Characteristics of patient-derived high-grade glioma cell cultures.
  • Table S11 (Microsoft Excel format). Original numerical data for experiments presented as composite graphs.