Table 1.
Drugs and compounds for targeting of MYCN signaling.
| Inhibitor | Tumor type | Target | Phase | Reference |
|---|---|---|---|---|
| Direct MYC/MYCN inhibitors | ||||
| Omomyc | Glioma, ATRT | MYC proteins | Preclinical | (1–5) |
| MYCMI-6 | Various cancers, NB | MYC proteins | Preclinical | (6) |
| Inhibitors of MYCN transcriptional machinery | ||||
| JQ1 I-BET |
Various cancers, MB, and NB | BRD4 | Preclinical | (7–10) (11) |
| Zotiraciclib | GBM | CDK9 | Clinical orphan drug | (12) |
| Enniatin B | N/A | MYCN | Biochemical | (13) |
| MZ1 | N/A | BRD4 | Biochemical | (14) |
| A1874 | Colon cancer, lung cancer, osteosarcoma | BRD4 | Preclinical | (15) |
| Cell cycle related inhibitors targeting MYCN | ||||
| Palbociclib | MB, NB | CDK4/6 | Preclinical | (9, 16, 17) |
| Abemaciclib | DIPG, brain tumor (NOS), NB, ATRT | CDK4/6 | Clinical trial | (19), NCT02644460, NCT03220646 |
| Milciclib | MB | CDK2 | Preclinical | (9) |
| Thymic carcinoma | Clinical trial | NCT01011439 | ||
| Alisertib | GBM, MB, NB | Aurora A | Preclinical | (20–23) |
| High-risk AML | Clinical trial | NCT02560025 | ||
| PI3K/AKT/mTOR inhibitors targeting MYCN | ||||
| PIK-75, PW-12 | MB | PI3K | Preclinical | (24) |
| Rapamycin | NB | mTORC1 | Preclinical | (25) |
| Temsirolimus | NB | mTORC1 | Preclinical | (25) |
| CNS tumors | Clinical trial | NCT00003712 | ||
| NVP-BEZ235 | MYCN-dependent tumors | mTORC1/2, PI3K | Preclinical | (26) |
| Breast cancer | Clinical trial | NCT00620594 | ||
| Everolimus | Breast cancer | mTORC1 | Clinical trial | NCT01783444 |
| Pediatric epilepsy | Approved | (27) | ||
| Sapanisertib | MB | mTORC1/2, PI3K | Preclinical | (28) |
| Ribosome biosynthesis inhibitors targeting MYCN | ||||
| Quarfloxin, CX-5461 | MYCN-driven NB | RNA Polymerase I | Preclinical | (29) |
A list of a selection of drugs or compounds identified as potential direct or indirect targets of MYC/MYCN-driven CNS/PNS tumors. Compounds in the clinical development for another tumor type (and not for brain tumors/CNS tumors) are mentioned in cases where they showed promising results in preclinical CNS tumor models.