Table 1.
Pre-clinical studies and clinical trials evaluating the use of compounds for the direct or indirect inhibition of MYC protein.
| Target | Compound | Malignancy | Phase | Trial number | Main adverse effects |
|---|---|---|---|---|---|
| MYC-MAX | Omomyc | Advanced solid tumors. | Phase I/II | NCT04808362 | - |
| KJ-Pyr-9 | Breast cancer xenografts. | Pre-clinical | |||
| SaJM589 | B cell line P493-6, Ramos (Burkitt's lymphoma cell line), HL-60 and KG1a (acute myeloid leukemia cell lines). | Pre-clinical | |||
| MYCMI-6 | Neuroblastoma | Pre-clinical | |||
| KSI-3716 | Bladder cancer xenograft. | Pre-clinical | |||
| MAX:MAX | KI-MS2-008 | T-cell acute lymphoblastic leukemia and hepatocellular carcinoma mouse models. | Pre-clinical | ||
| Aurora A kinase | MLN8237/ Alisertib | Relapsed/Refractory peripheral T-cell lymphoma, non-Hodgkin lymphoma, advanced-non hematological malignancies, lung, breast, head and neck, gastroesophageal malignancies, and advanced or metastatic sarcoma. | Phase I/II/III |
NCT01482962 NCT00807495 NCT01045421 NCT01653028 |
Neutropenia, anemia or gastrointestinal disorders. |
| CD532 | Neuroblastoma xenografts. | Pre-clinical | |||
| PLK1 | BI6727 (Volasertib) | Ovarian cancer. | Phase II | NCT01121406 | Anemia, neutropenia and thrombocytopenia. |
| PP2A | DT-061/(AZD6244) | KRAS-driven lung cancer mouse models, lung adenocarcinoma xenografts, non-small cell lung cancer xenografts. | Pre-clinical | ||
| FTY720 | leukemia, colon cancer, non-small cell lung cancer, breast cancer, hepatocellular carcinoma, prostate cancer. | Pre-clinical | |||
| OP449 | AML, breast cancer, and pancreatic cancer. | Pre-clinical | |||
| Perphenazine | Brain, breast, colon, pancreatic, liver, skin and lung cancer, ovarian and oral carcinoma and leukemia and lymphoma cell lines. T-ALL and melanoma xenografts. | Pre-clinical | |||
| LB-100 | Myelodysplastic syndromes, extensive stage lung small-cell carcinoma and astrocytoma, glioblastoma multiforme, giant cell glioblastoma, glioma and oligodendrogliomas. | Phase I/II |
NCT03886662 NCT04560972 NCT03027388 |
- | |
| Pin-1 | KPT-6566 | Pancreatic, lung, prostate, and breast cancer cell lines. Lung cancer xenografts. | Pre-clinical | ||
| ATRA | Advanced adenoid cystic carcinoma, pancreatic ductal adenocarcinoma, breast cancer. | Phase I/II |
NCT03999684 NCT03307148 NCT04113863 |
-** | |
| BJP-06-005-3 | Pancreatic ductal adenocarcinoma. | Pre-clinical | |||
| Sulfopin | Neuroblastoma and pancreatic mouse model, and neuroblastoma zebrafish model. | Pre-clinical | |||
| PIM1 | AZD1208 | Acute myelogeneous leukemia and advanced solid malignancies including malignant lymphoma. | Phase I |
NCT01489722 NCT01588548 |
Guillain–Barré syndrome, increased blood creatinine, neutropenia, anemia and gastrointestinal disorders. |
| TP-3654 | Advanced solid tumors. | Phase I | NCT03715504 | - | |
| PIM447 | Myelofibrosis, acute myeloid leukemia, high risk myelodysplastic syndrome, multiple myeloma. | Phase I |
NCT02370706 NCT02078609 NCT01456689 NCT02160951 |
Thrombocytopenia, anemia or fatigue. | |
| SGI-1776 | Refractory prostate cancer and relapsed/refractory non Hodgkin's lymphoma, relapsed/refractory leukemias, | Phase I/II |
NCT00848601 NCT01239108 |
Cardiac toxicity. | |
| SEL24/MEN1703 | Acute myeloid leukemia. | Phase I/II | NCT03008187 | - | |
| SKP2 | SZL-P1-41 | Prostate and long tumor xenografts. | Pre-clinical | ||
| Dioscin | Colorectal adenocarcinoma xenografts. | Pre-clinical | |||
| FKA | Synovial sarcoma, osteosarcoma xenografts and prostate cancer in vivo models. | Pre-clinical | |||
| SKPin C1 | Uveal melanoma xenografts. | Pre-clinical | |||
| BRD4 (and other BET proteins) | OTX015/MK-8628 | Acute leukemia, solid tumors. | Phase I/II |
NCT02698189 NCT02698176 NCT02296476 NCT02259114 NCT01713582 |
Thrombocytopenia, anemia or gastrointestinal disorders. |
| GSK2820151 | Solid tumors. | Phase I | NCT02630251 | -* | |
| ZEN-3694 | Metastatic castration-prostate cancer and triple-negative breast cancer. | Phase I/II |
NCT02705469 NCT02711956 NCT03901469 |
Eye disorders, nausea or fatigue. | |
| CPI-0610 | Lymphoma, multiple myeloma, myelofibrosis leukemia, myelocytic, acute myelodysplastic/myeloproliferative neoplasm myelodysplastic syndrome (MDS). | Phase I/II |
NCT02158858 NCT01949883 NCT02157636 |
Gastrointestinal disorders, fatigue, anemia or thrombocytopenia. | |
| GSK525762/I-BET762 | Hematological malignancies. | Phase I/II |
NCT01943851 NCT01587703 |
Thrombocytopenia and gastrointestinal events. | |
| INCB057643 | Any advanced malignancy. | Phase I/II | NCT02711137 | Nausea, thrombocytopenia or fatigue. | |
| JQ1 | Multiple myeloma, T-ALL, B-ALL, acute myeloid leukemia cell lines. Medulloblastoma, glioblastoma, neuroblastoma, colorectal carcinoma and breast cancer cells. | Pre-clinical | |||
| USP7 | P22077 | Neuroblastoma and hepatocellular carcinoma xenografts. | Pre-clinical | ||
| XL177A | Ewing Sarcoma, acute myeloid leukemia, and multiple myeloma cell lines. | Pre-clinical | |||
| GNE-6640 | Acute myeloid leukemia cell lines and eosinophilic leukemia xenografts. | Pre-clinical | |||
| GNE6776 | Eosinophilic leukemia xenografts. | Pre-clinical | |||
| FT671 | Multiple myeloma xenografts. | Pre-clinical | |||
| HUWE1 | BI8622/ BI8626 | Multiple myeloma cell-lines and in vivo models. | Pre-clinical | ||
| Aurora B kinase | Acute myeloid leukaemia and advanced solid malignancies. |
NCT00497731 NCT00497991 |
Neutropenia, leukopenia, gastrointestinal disorders or stomatitis. | ||
| HUWE1 | BI8622/ BI8626 | Multiple myeloma cell-lines and in vivo models. | Pre-clinical | ||
| HDAC-(PI3K) | CUDC-907 | multiple myeloma, lymphoma, thyroid cancer and in solid tumors. | Phase I/II |
NCT02674750 NCT01742988 NCT02909777 NCT03002623 |
Gastrointestinal events or thrombocytopenia, lymphopenia, leukopenia or anemia. |
⁎
Only1/2 patients per group.