Investigational approaches (selection)
| Mode of action . | Agent(s) . | Phase . | Target(s) . |
|---|---|---|---|
| Third-generation TKI | Ponatinib53 | II | Pan-BCR-ABL including T315I |
| DCC-203672 | I | Abl-switch pocket | |
| PP2A activation | Fingolimod (FTY720)75 | Preclinical | PP2A |
| SET antagonist OP44976 | Preclinical | SET | |
| CIP2A inhibitor74 | Preclinical | CIP2A | |
| Survival of LSCs | BCL6 + TK inhibitors78 | Preclinical | BCL6 + BCR-ABL |
| HIF1α inhibitor80 | Preclinical | HIF1α | |
| IL1 RAP antibodies86 | Preclinical | IL1 RAP | |
| Smoothened inhibitors in combination with TKI83 (dasatinib, nilotinib) | Preclinical | Smoothened (hedgehog pathway) + BCR-ABL | |
| Jak2 inhibitor + dasatinib85 | Preclinical | Jak2 + BCR-ABL, LSC | |
| Activation of apoptosis | BCL2-inhibitor ABT-73788 | Preclinical | Antiapoptotic proteins |
| Triptolide87,88 | Preclinical | Antiapoptotic proteins | |
| Dual-kinase inhibitor ON04458091 | Preclinical | BC, T315I | |
| MEK inhibitor PD184352 + farnesyltransferase inhibitor BMS-21466289 | Preclinical | MEK1, MEK2, RAS | |
| Others | Omacetaxine92 | II / III | BCR-ABL, T315I, BC |
| Mode of action . | Agent(s) . | Phase . | Target(s) . |
|---|---|---|---|
| Third-generation TKI | Ponatinib53 | II | Pan-BCR-ABL including T315I |
| DCC-203672 | I | Abl-switch pocket | |
| PP2A activation | Fingolimod (FTY720)75 | Preclinical | PP2A |
| SET antagonist OP44976 | Preclinical | SET | |
| CIP2A inhibitor74 | Preclinical | CIP2A | |
| Survival of LSCs | BCL6 + TK inhibitors78 | Preclinical | BCL6 + BCR-ABL |
| HIF1α inhibitor80 | Preclinical | HIF1α | |
| IL1 RAP antibodies86 | Preclinical | IL1 RAP | |
| Smoothened inhibitors in combination with TKI83 (dasatinib, nilotinib) | Preclinical | Smoothened (hedgehog pathway) + BCR-ABL | |
| Jak2 inhibitor + dasatinib85 | Preclinical | Jak2 + BCR-ABL, LSC | |
| Activation of apoptosis | BCL2-inhibitor ABT-73788 | Preclinical | Antiapoptotic proteins |
| Triptolide87,88 | Preclinical | Antiapoptotic proteins | |
| Dual-kinase inhibitor ON04458091 | Preclinical | BC, T315I | |
| MEK inhibitor PD184352 + farnesyltransferase inhibitor BMS-21466289 | Preclinical | MEK1, MEK2, RAS | |
| Others | Omacetaxine92 | II / III | BCR-ABL, T315I, BC |
LSC indicates leukemia stem cell; and MEK, mitogen-activated protein kinase kinase.