Table 1 Summary of available inhibitors which target self-renewal pathways involved in myeloid malignancies
From: Targeting self-renewal pathways in myeloid malignancies
Pathway | Name of drug | Mode of action | Producer | Stage of clinical / non-clinical development | Trial number |
|---|---|---|---|---|---|
Aspirin / NSAIDs | Complex / chemoprevention | Generic | Over the counter medications; no ongoing clinical | Â | |
Vitamin A | Reduce TCF-β-catenin | Generic | trials in haematological malignancies | ||
Non-clinical | |||||
Vitamin D | complex formation | Leo | Non-clinical | ||
(EB1089) | Binding of β-catenin by | Pharmaceuticals |  | ||
WNT1 and WNT2 | vitamin D receptor | Â | Non-clinical | ||
McAbs | Monoclonal antibodies | Generic | Â | ||
XAV939 | Â | Â | Non-clinical | ||
ZTM000990, | Inhibits tankyrase 1&2 | Novartis | Non-clinical | ||
PKF118-310, PKF118-744, PKF222-815, CGP049090, PNU-74654 ICG-001 NSC668036 SB-216763 | Inhibit TCF-β-catenin | Multiple Institute for Chemical Genomics | Non-clinical Non-clinical | ||
NCI | Non-clinical | ||||
| Â | complex | Â | Â | ||
Inhibits β-catenin/CREB-binding protein transcription | |||||
Inhibits dishevelled PDZ domain | |||||
| Â | Inhibits GSK-3 | Sigma | Â | ||
GSK-3IX, | Â | Chemicals | Non-clinical | ||
| Â | Inhibit GSK-3 | EMD | Â | ||
alsterpaullone | Â | Biosciences | Â | ||
MK-0752 | γ-secretase inhibitor | Merck | Phase 1: T acute lymphoblastic leukemia | NCT00100152 | |
GSI-I, GSI-IX, GSI- | γ-secretase inhibitors | Calbiochem | Non-clinical | ||
X, GSI-XII, GSI- | Monoclonal antibody | Generic | Non-clinical | ||
XXI | |||||
NOTCH3 McAb | |||||
Hh[34] | Cyclopamine | SMO antagonist | Generic | Non-clinical | Â |
|  | LDE225 | SMO antagonist | Novartis | Phase 1: CML – in combination with Nilotinib | NCT1456676 |
LEQ506 | SMO antagonist | Novartis | Solid tumours only (phase I & II) | Â | |
GDC-0449 | SMO antagonist | Genentech | Phase 1b: Myeloma in first remission or first relapse post ASCT | NCT01330173 | |
BMS-833923 | SMO antagonist | Bristol-Myers Squibb | Phase 1: CML - in combination with Dasatinib | NCT01218477 | |
Phase 1b: Myeloma - in combination with Lenalidomide with Dexamethasone or Bortezomib with Dexamethasone | NCT00884546 | ||||
| Â | IPI926 | SMO antagonist | Infinity | Phase 2: Myelofibrosis | NCT01371617 |
PF-04449913 | SMO antagonist | Pfizer | Phase 1: CML - in combination with Dasatinib or Bosutinib | NCT00953758 | |
GANT61 | Direct GLI inhibition | Generic | Non-clinical | Â | |
FOXO/TGFβ[35] | Rapamycin | Inhibitor of mTOR | Generic | No current clinical trials in haematological malignancies | |
LY294002 | PI3K inhibitor | ||||
LY364947 | PI3K inhibitor | Merck | Non-clinical | ||
Merck | Non-clinical | ||||
C-MYB[36] | C-MYB AS ODN | Infusional C-MYB anti-sense oligodeoxy nucleotides | University of Pennsylvannia | Phase 1 - In Advanced Hematological Malignancies | NCT00780052 |