Table 1.
NOTCH1 pathway targeting strategies.
| Inhibitor | Target | Mechanism | References |
|---|---|---|---|
| P2207, P217564 | USP7 | Small molecule inhibiting USP7-dependent NOTCH1 deubiquitination |
[6,7] |
| PF-0308414 | γ-secretase complex | Small molecule inhibiting γ-secretase dependent NOTCH1 cleavage |
[64,68,70] |
| RO4929097 | γ-secretase complex | Small molecule inhibiting γ-secretase dependent NOTCH1 cleavage |
[64,68] |
| AL101/AL102 | γ-secretase complex | Small molecule inhibiting γ-secretase dependent NOTCH1 cleavage |
[64,68,69] |
| OMP-52M51 (Brontictuzumab) |
NOTCH1 | Antibody interfering with NOTCH1-ligand interaction |
[71] |
| Mab604.107 | NOTCH1 | Antibody interfering with NOTCH1-ligand interaction |
[72] |
| Demcizumab | DLL4 | Antibody interfering with NOTCH-DLL4 ligand interaction |
[73] |
| Enoticumab | DLL4 | Antibody interfering with NOTCH-DLL4 ligand interaction |
[74] |
| ZLDI-8 | ADAM17 | Small molecule inhibiting ADAM17-dependent NOTCH1 cleavage |
[79] |
| NOTCH decoys | NOTCH1 | Soluble inhibitors interfering with NOTCH1-ligand interaction | [80] |
| SAHM | MAML1 | Stapled α-helical peptides interfering with MAML1 binding to NOTCH transcriptional complex |
[81] |
| NADI-351 | NOTCH Ternary complex (NTC) | Small molecule disrupting NTC | [82] |
| Thapsigargin | SERCA | Small molecule inhibiting SERCA activity | [83] |
| CAD204520 | SERCA | Small molecule inhibiting SERCA activity | [84] |
| 6-alkynyl and 6-alkenyl fucose |
POFUT1 | L-fucose analogs disrupting NOTCH1-DELTA-ligand interactions |
[85] |