Table 1.
Inhibitory potencies of compounds against all catalytically active subunits (β5i, β2i, and β1i) of the iCP and against all catalytically active subunits (β5, β2, β1) of the human cCP. In the assays, the following substrates were used: Suc-LLVY-AMC for β5i and β5; Boc-LRR-AMC for β2i and β2; Ac-PAL-AMC for β1i; Ac-nLPnLD-AMC for β1.
| Cpd | β5i (RA [%]) 1 |
β2i (RA [%]) 1 |
β1i (RA [%]) 1 |
β5 (RA [%]) 1 |
β2 (RA [%]) 1 |
β1 (RA [%]) 1 |
|---|---|---|---|---|---|---|
| 4 | 78 ± 5 | 100 ± 0 | 95 ± 24 | 80 ± 21 | 82 ± 7 | 88 ± 0 |
| 7 | 76 ± 3 | 100 ± 0 | 87 ± 15 | 81 ± 18 | 86 ± 7 | 88 ± 5 |
| 8 | 70 ± 0 | 100 ± 0 | 90 ± 21 | 78 ± 21 | 87 ± 7 | 89 ± 2 |
| 9 | 69 ± 13 | 109 ± 3 | 76 ± 7 | 72 ± 18 | 90 ± 2 | 99 ± 5 |
| 10 | 62 ± 5 | 102 ± 2 | 87 ± 19 | 79 ± 20 | 86 ± 2 | 90 ± 3 |
| 11 | 76 ± 12 | 109 ± 14 | 72 ± 8 | 66 ± 21 | 89 ± 4 | 87 ± 2 |
| 15 | 71 ± 1 | 103 ± 4 | 94 ± 16 | 76 ± 20 | 87 ± 3 | 97 ± 2 |
| 16 | 65 ± 3 | 107 ± 3 | 92 ± 21 | 77 ± 19 | 83 ± 4 | 83 ± 2 |
| 20 | 78 ± 0 | 88 ± 0 | 83 ± 18 | 76 ± 17 | 81 ± 6 | 79 ± 5 |
| 21 | 76 ± 1 | 90 ± 0 | 81 ± 10 | 79 ± 14 | 80 ± 4 | 86 ± 4 |
| 23 | 74 ± 11 | 113 ± 7 | 72 ± 1 | 72 ± 12 | 89 ± 6 | 92 ± 4 |
| 24 | 77 ± 7 | 109 ± 7 | 74 ± 5 | 63 ± 26 | 88 ± 5 | 89 ± 7 |
| carf. | 3 ± 1 | 1 ± 1 | 1 ± 1 | 0 ± 0 | 16 ± 6 | 2 ± 2 |
| ‘42’ | 5 ± 2 | 102 ± 5 | 97 ± 8 | 52 ± 4 | 99 ± 2 | 99 ± 8 |
1 RA values are means from at least three independent determinations. Ac-PAL-AMC, acetyl-Pro-Ala-Leu-7-amino-4-methylcoumarin; Ac-nLPnLD-AMC, acetyl-Nle-Pro-Nle-Asp-AMC; Boc-LRR-AMC, t-butyloxycarbonyl-Leu-Arg-Arg-7-amino-4-methylcoumarin; Suc-LLVY-AMC, succinyl-Leu-Leu-Val-Tyr-7-amino-4-methylcoumarin. carf.: carfilzomib.