TABLE 1
Various properties of JX401 and its derivatives
Compound | Structure | Effect on Growth (Growth Rate of Yeast Expressing p38α = 1) | p38α Activity In Vitro in the Presence of 1 μM Concentration of the Compound (No inhibition = 100% Activity) | IC50 | Efficiency in Blocking Myoblast Differentiationa | Toxicity to Mammalian Cellsb |
|---|---|---|---|---|---|---|
| % | nM | |||||
| JX-162 |
| 1.49 | 31.83 | 481.60 | N.D. | N.D. |
| JX-401 |
| 1.76 | 4.47 | 32.20 | ++ | Not toxic |
| Group A | ||||||
| B2 |
| 1.60 | 2.40 | 21.90 | ++ | Partially toxic |
| F8 |
| 1.09 | 6.10 | 35.70 | ++ | Toxicc |
| D4 |
| 1.77 | 8.00 | 71.00 | ++ | Not toxic |
| G5 |
| 1.86 | 9.70 | 63.60 | ++ | Not toxic |
| C7 |
| 1.93 | 10.70 | 100.90 | + | Not toxic |
| B7 |
| 1.24 | 13.30 | 125.30 | ++ | Partially toxic |
| F7 |
| 1.99 | 15.60 | 147.40 | + | Not toxic |
| C4 |
| 1.50 | 19.20 | 158.10 | + | Partially toxic |
| E3 |
| 1.76 | 22.40 | 240.20 | + | Not toxic |
| D6 |
| 1.71 | 26.70 | 394.40 | - | Not toxic |
| Group B | ||||||
| D3 |
| 0.69 | 32.00 | N.D. | - | Not toxic |
| E5 |
| 0.38 | 32.70 | N.D. | N.A. | Toxic |
| B5 |
| 0.23 | 40.50 | N.D. | N.A. | Toxic |
| G4 |
| 0.64 | 45.10 | N.D. | ++ | Partially toxic |
| F6 |
| 0.94 | 53.80 | N.D. | - | Not toxic |
| % | nM | |||||
| D7 |
| 0.38 | 63.80 | N.D. | N.A. | Toxic |
| F4 |
| 0.58 | 64.60 | N.D. | N.A. | Toxic |
| G7 |
| 0.53 | 72.60 | N.D. | ++ | Partially toxic |
| D2 |
| 0.49 | 74.20 | N.D. | ++ | Not toxic |
| G8 |
| 0.72 | 81.10 | N.D. | - | Not toxic |
| Group C | ||||||
| C2 |
| 0.34 | 104.30 | N.D. | N.A. | Toxic |
| G2 |
| 0.74 | 122.00 | N.D. | - | Not toxic |
| B8 |
| 0.87 | 154.60 | N.D. | + | Partially toxic |
| E4 |
| 0.53 | 155.20 | N.D. | - | Not toxic |
| D8 |
| 1.01 | 157.80 | N.D. | N.A. | Toxic |
| C8 |
| 0.74 | 182.30 | N.D. | - | Not toxic |
| C3 |
| 0.03 | 236.10 | N.D. | + | Not toxic |
-
N.D., not determined; N.A., could not be assessed because of a massive cell death; ++, efficient blocker; +, partial blocker; -, nonblocker.
-
↵ a Determined by the appearance of myotubes under the microscope and/or by expression levels of myogenin.
-
↵ b Determined by the appearance of intact/floating cells under the microscope.
-
↵ c Did not cause cell death, but cells were unable to differentiate after removal of the drug.