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 | [129, 130] | |
| 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 | [113, 118, 121, 131, 132] |
| 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 | [118, 122] | |
| 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 | [125, 127, 128] |
| 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 | [123, 124] | |
| 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 | [134–136] |
| 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” |
[137–139] | |
| MSI-2 | 4.7 ± 0.5 µM |