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.