Table 2 Summary of Musashi inhibitors and their effects and functions
Inhibitor | target | KD | tested in | Effect after treatment | additional targets | comment | source |
|---|---|---|---|---|---|---|---|
Aza-9 | MSI-1 | 1.2 µM | Colon cancer cell lines | Inhibited proliferation, induced apoptosis / autophagy G1 accumulation | HuR | ||
MSI-2 | 0.5 µM | ||||||
(-) gossypol | MSI-1 | 476 ± 273 nm | Colon cancer cell lines Breast cancer cell lines Pancreatic cancer cells | Reduced Notch/Wnt signaling Increased apoptosis/autophagy, reduced tumor growth in xenografts Reduced proliferation, damaged cell membrane integrity Triggered apoptosis and suppression of spheroid formation | BCL-2 family MDM2 | Different clinical trials were performed | |
Gossypolone | MSI-1 | 13 ± 5 nm | Colon cancer cell lines Breast cancer cell line | Inhibited proliferation Induced apoptosis/autophagy, Inhibited tumor growth of human colon cancer cell xenografts in nude mice Suppression of DNA synthesis | BCL-2 family | ||
MSI-2 | 7 ± 0.3 nm | ||||||
Ro 08-2750 | MSI-1 | N.a. | Bone marrow cells Murine leukemia model Chronic lymphatic leukemia | Reduced cell proliferation, increased apoptosis Reduced colony formation Reduction of viable cells | Inhibits NGF with lower KD (1.7 µM) | SRF2 and SYNCRIP proteins are bound with 15–20 x higher KD | |
MSI-2 | 12.3 ± 0.5 µM | ||||||
Largazole | MSI-2 | Lung cancer and CML cell lines | Inhibited proliferation and induced apoptosis, suppressed colony formation | The amount of MSI2 mRNA is reduced after treatment | [133] | ||
Luteolin | MSI-1 | 3.2 ± 0.02 µM | Glioblastoma cell lines | Inhibited proliferation, migration, colony formation and invasion | Reduces oxidative stress | ||
Palmatine | MSI-1 | 17 µM Kd (in vitro) 26.4 µM Kd (in cellular protein based assays) | Colon cancer cell line and xenograft model | Reduced cell growth Reduced tumor growth in mice Multiple anti-cancer functions | rpS6/NFkB/FLIP axis AURKA | First three days of treatment resulted in weight loss in mice | |
MSI-2 | 67.5 µM Kd (in cellular protein based assays) | ||||||
oelic acids | MSI-1 | 1.2 ± 0.4 µM | HeLa Mouse model | Increased amount of miR-7 (tumor suppressor) in vitro Increased fibrosis and apoptosis in kidneys after injection | Erucic acid binds with even higher affinity to MSI1 “Musashi1 appears to act as a `nutrient sensor` turning up its activity when oleic levels are low and vice versa” | ||
MSI-2 | 4.7 ± 0.5 µM |