Table 1.
Summary of the Signalling Pathway Inhibitors and Their Characteristics
| Signalling pathway | Drug name (or alias) | Primary targets and (IC50, in vitro trial) | Cancer type | Phase | Formula | Ref. |
|---|---|---|---|---|---|---|
| Wnt signalling pathway | LGK-974 (WNT974) | Porcn (0.4 nM) | breast cancer, cutaneous squamous cell carcinoma, glioblastoma | Phase I | C23H20N6O | (27-30) |
| ICG-001(PRI-724) | CBP (3 μM) | melanoma, gastric cancer, leukaemia oral squamous cell carcinomas, TNBC | Phase I | C33H32N4O4 | (32-35) | |
| Ipafricept (OMP-54F28) | Wnt ligand | solid tumours, hepatocellular carcinoma, ovarian cancer, pancreatic cancer |
Phase I | - | (36-38) | |
| Notch signalling pathway | DAPT (GSI-IX) | γ-secretase (Aβ) (20 nM) | osteosarcoma, leukaemia, ovarian cancer | Phase II | C23H26F2N2O4 | (48-50) |
| MK-0752 | γ-secretase (Aβ40) (5 nM) | breast cancer | Phase I | C21H21ClF2O4S | (51) | |
| Demcizumab (OMP-21M18) | Notch ligand | head and neck squamous cell carcinoma | Phase I | - | (54-56) | |
| Hh signalling pathway | Cyclopamine | Smoothened (Smo) (46 nM) | pancreatic cancer, bladder tumour | Phase I | C27H41NO2 | (66-68) |
| Vismodegib (GDC-0449) | Hedgehog (3.0 μM) | basal cell carcinoma, pancreatic cancer, small-cell lung cancer, prostate cancer, glioblastoma | Phase IV | C19H14Cl2N2O3S | (71, 73, 75) | |
| GANT61 | GLI1/GLI2 (5 μM) | breast cancer, pancreatic cancer | preclinical | C27H35N5 | (78-80) | |
| TGF-β signalling pathway | LY2109761 | TβRI/II (38 nM/300 nM) | pancreatic cancer colorectal cancer, hepatocellular carcinoma, glioblastoma | preclinical | C26H27N5O2 | (93-96) |
| Galunisertib (LY2157299) | TβRI (56 nM) | hepatocellular carcinoma | Phase I/II | C22H19N5O | (98) | |
| JAK/STAT3 signalling pathway | Ruxolitinib (INCB018424) | JAK1/2 (3.3 nM/2.8 nM) | myelofibrosis, polycythemia vera, myxoid liposarcoma | Phase II | C17H18N6 | (102, 103) |
| Napabucasin (BBI608) | Stat3 (0.291~1.19 μM) | gastrointestinal malignancies, biliary tract cancer, colorectal cancer | Phase III | C14H8O4 | (105-107) | |
| Nf-κB signalling pathway | GTCpFE | IKKα/β phosphorylation (20 μM) | breast cancer | preclinical | - | (113, 114) |
| BMS-345541 | IKK-2/ IKK-1 (0.3 μM/4 μM) | leukaemia, lung cancer, breast cancer | preclinical | C14H17N5 | (116-118) | |
| Multiple pathways | EC-70124 | - | breast, colorectal, prostate tumours, acute myeloid leukaemia | preclinical | C26H19N3O | (119-122) |
| Niclosamide | STAT3 (0.7 μM) | breast cancer, colorectal cancer, oral cancer | Phase I/II | C13H8Cl2N2O4 | (124, 126-129) |
Abbreviations: CBP, cAMP-response element-binding (CREB) binding protein; TβR, TGFβ receptor; TNBC, Triple negative Breast Cancer.