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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

Wnt/GSK3β[2632]

Aspirin / NSAIDs

Complex / chemoprevention

Generic

Over the counter medications; no ongoing clinical

 

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

 

Non-clinical

McAbs

Monoclonal antibodies

Generic

 

XAV939

  

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

 

complex

  

Inhibits β-catenin/CREB-binding protein transcription

Inhibits dishevelled PDZ domain

 

Inhibits GSK-3

Sigma

 

GSK-3IX,

 

Chemicals

Non-clinical

 

Inhibit GSK-3

EMD

 

alsterpaullone

 

Biosciences

 

Notch[32, 33]

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

 
 

LDE225

SMO antagonist

Novartis

Phase 1: CML – in combination with Nilotinib

NCT1456676

LEQ506

SMO antagonist

Novartis

Solid tumours only (phase I & II)

 

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

 

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

 

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