Table I.
List of hedgehog pathway inhibitors used in GBM.
| Inhibitor name | Drug combination | Target | Mode of action | Reverse resistance | (Refs.) |
|---|---|---|---|---|---|
| Dynarrestin | (−) | PC | Inhibition of the flow of SMO in PC | (−) | (112) |
| O6-benzylamine | Honokiol(+) | SHH | Antagonist of MGMT | (+) | (117) |
| LDE225 | (−) | SHH | Downregulated PTCH1 and GLI1 | (−) | (120) |
| PEI-SNAs | (−) | GLI1 | Binding to clearance receptors on GBM cells | (+) | (123) |
| GANT-61 | TMZ | SHH | Increases production of ROS | (+) | (124) |
| GANT-61 | (−) | SHH | Increases the expression of LC3 II and cleaved caspase 3 and 9 | (−) | (125) |
| Curcumin | MicroRNA-326 | SHH/GLI1 | Antagonist of SHH/GLI1 | (−) | (126) |
| XH30 | (−) | GLI1 | Decreases GLI1 activity | (+) | (127) |
| Phosphorylated peptides | (−) | GLI2 | Decreases GLI2 activity | (−) | (128) |
| Tubasatin A | (−) | SHH/GLI1 | Downregulation of GLI1 and PTCH1/2 receptors | (−) | (129,130) |
| CGP-2 | (−) | GLI1 | Antagonist of SMO | (−) | (132) |
| Capsulated | TMZ | GLI1 | Inhibition of GLI1 expression | (+) | (136) |
| propylamine PF403 | (−) | SMO/GLI1 | Antagonist of SMO/GLI1 | (+) | (137) |
PC, primary cilia; TMZ, temozolomide; SMO, smoothened; MGMT, methylguanine methyltransferase; PEI-SNAs, polyethylene imine-coated spherical nucleic acid nanoparticles; ROS, reactive oxygen species; CGP-2, cyclodopamine glucuronoside precursor drugs; PF403, 13A (S)-3-hydroxyl-6,7-dimethoxyphenanthro[9,10-b]-indolizidine; Gli, glioma-associated oncogene; GBM, glioblastoma; SHH, Sonic Hedgehog; PTCH, patched; LC, light chain.