Table 1.
Summary of NOS inhibition for relevant compounds
| Inhibition (μM) |
|||||
|---|---|---|---|---|---|
| Compound | |||||
| iNOS | eNOS | nNOS | Reference | Notes | |
| 1 | 1.4 (human, Ki) | 0.06 (human, Ki) | 0.09 (human, Ki) | 123 | For the acid form, L-NAME is only a weak inhibitor |
| 2 | 2.6 (human, Ki) | 0.7 (human, Ki) | 1.7 (human, Ki) | 123 | Values for competitive inhibition |
| 3 | 2.2 (murine, IC50) 3.9 (murine, Ki) |
3.9 (bovine, Ki) | 3.9 (rat, IC50) 1.7 (rat, Ki) |
123, 128 | Values for competitive inhibition; also a mechanism-based inactivator |
| 4 | 54±58 (murine, IC50) | Not reported; in vivo results suggest selectivity | 160 (rat, IC50) | 131,132 | Little selectivity later reported |
| 5 | 3.3 (murine, IC50) 0.9 (human, Ki) |
16 (human, Ki) | 92 (rat, IC50) 10 (human, Ki) |
128, 123 | Values for competitive inhibition |
| 6 | >1850 (human, IC50) | 2420 (human, IC50) | >1850 (human, IC50) | 138 | Is a prodrug; hydrolyzes to 5, little inhibitory activity |
| 7 | 2.19±0.23 (human, IC50) <40 nM (human, Kd) |
554±61 (human, IC50) | 177±44 (human, IC50) | 7 | Time and NADPH-dependent competitive inhibitors |
| 8 | 9.03±0.85 (human, IC50) <90 nM (human, Kd) |
>1000 (human, IC50) | 719±179 (human, IC50) | 7 | Time and NADPH-dependent competitive inhibitors |
| 9 | 2.9 (human, IC50) | Exact value not reported; around 25-fold weaker | Exact value not reported; around 5-fold weaker | 144 | Time-dependent, irreversible inhibitor |
| 10 | 100 (species not specified, IC50) | Exact value not reported; in vivo assays suggest no eNOS inhibition | Exact value not reported; selectivity is reported to be 8-fold | 149 | |
| 11 | 130 (species not specified, IC50) | Exact value not reported; in vivo assays suggest no eNOS inhibition | 180 (species not specified, IC50) | 148 | Molecular modeling suggests competitive inhibition. |
| 12 | 0.047 (human, Ki) | 9.0 (human, Ki) | 0.25 (human, Ki) | 150 | Proposed to be a competitive inhibitor |
| 13 | 0.007 (human, Kd) | 50 (human, Ki) | 2.0 (human, Ki) | 151 | Originally proposed to be irreversible or a very slow reversible inhibitor |
| 14 | 0.20±0.03 (presumably human, IC50) | 350±70 (presumably human, IC50) | Not reported | 154 | Competitive inhibitor |
| 15 | 1.0 (human, IC50) | 4.7 (human, IC50) | 1.1 (human, IC50) | 155 | Competitive inhibitor |
| 16 | 0.0019 (human, Ki) | 0.018 (human, Ki) | 0.0037 (human, Ki) | 156, 157 | Competitive inhibitor like 15. |
| 17 | 0.25 (human, IC50) | 226 (human, IC50) | 3.2 (human, IC50) | 160 | |
| 18 | 0.78 (human, IC50) | 1980 (human, IC50) | 27 (human, IC50) | 161 | |
| 19 | 0.16 (human, IC50) |
No significant effect at 100 μM (human) |
16 (rat, IC50) | 162 | |
| 20 | 0.037 (human, IC50) | >100 (human, IC50) | 1 (human, IC50) | 163 | Competitive inhibitors. |
| 21 | 0.4 (human, IC50) | 50 (human, IC50) | 1 (human, IC50) | 166 | X-ray crystallography indicates competitive inhibitors. |
| 22 | 0.17 (human, IC50) | 0.072 (human, IC50) | 0.074 (human, IC50) | 167 | |
| 23 | 0.028 (human, IC50) | 0.15 (human, IC50) | 0.10 (human, IC50) | 167 | |
| 24 | 0.071 (human, IC50) | >100 (human, IC50) | 6.6 (human, IC50) | 169 | |
| 25 | 0.086 (human, IC50) | 162 (human, IC50) | 17 (human, IC50) | 170, 171 | Competitive, time-dependent, irreversible inhibitor. |
| 26 | 7.3±1 (possibly murine, spectral binding constant for iNOS monomer) | Not reported | Not reported | 174 | Dimerization inhibitor |
| 27 | 0.028 (human, IC50, cell lysate) 0.0022 (human, Ki, purified iNOS monomer) |
32 (human, IC50, cell lysate) | 0.140 (human, IC50, cell lysate) | 175 | Dimerization inhibitor |
| 28 | 0.00029 (human, IC50, A172 cell lysate) | Selectivity reported to be >5000-fold (vaccinia-transfected cell lysate | Selectivity reported to be 62-fold (vaccinia-transfected cell lysate | 178 | Different selectivity values depending on whether vaccinia transfection or tetracycline induction is used |
| 29 | 1.3 (human, EC50, cell-based) 46 (murine, EC50, cell-based) |
>100 (human, EC50, cell-based) | >10 (human, EC50, cell-based) | 179 | Dimerization inhibitor |
| 30 | 0.011 (human, EC50, cell-based) 0.12 (murine, EC50, cell-based) |
26 (human, EC50, cell-based) | 2.3 (human, EC50, cell-based) | 179 | Dimerization inhibitor |
| 31 | 0.009 (human, EC50, cell-based) 0.034 (murine, EC50, cell-based) |
6.1 (human, EC50, cell-based) | 0.36 (human, EC50, cell-based) | 179 | Dimerization inhibitor |
| 32 | 0.091 (human, EC50, cell-based) | 16.5 (human, EC50, cell-based) | 0.30 (human, EC50, cell-based) | 181 | Dimerization inhibitor |
| 33 | ~0.003 (species not specified, IC50) | >30 (species not specified, IC50) | ~2.4 (species not specified, IC50) | 182 | Dimerization inhibitor |
| 34 | Not reported, but lowers iNOS expression in PC12 cell cultures | Not reported | Not reported | 56 | Exact mechanism of action unknown; possibly multiple targets |
| 35 | Inhibits NO production in LPS-stimulated macrophages at 20 μM | Not reported | Not reported | 200 | Exact mechanism of action unknown; proposed to be a competitive inhibitor |