Table 1.
Potencies of all compounds tested as inhibitors of prostanoid formation determined in the COX-1 assay, WBA-COX-2, and WHMA-COX-2
| Compound | COX-1
|
WBA-COX-2
|
WHMA-COX-2
|
IC50 ratios
|
IC80 ratios
|
Ranking at IC80 ratios
|
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| IC50, μM | IC80, μM | IC50, μM | IC80, μM | IC50, μM | IC80, μM | WBA COX-1 | WHMA COX-1 | WBA COX-1 | WHMA COX-1 | WBA COX-1 | WHMA COX-1 | |
| 6MNA | 42 | 130 | 146 | 580 | n.d. | n.d. | 3.5 | n.d. | 4.5 | n.d. | 27 | n.d. |
| Aspirin | 1.7 | 8.0 | >100 | >100 | 7.5 | 30 | >100 | 4.4 | >100 | 3.8 | 34 | 23 |
| Carprofen | 0.087 | 19 | 4.3 | 75 | n.d. | n.d. | 50 | n.d. | 3.9 | n.d. | 25 | n.d. |
| Diclofenac | 0.075 | 1.0 | 0.038 | 0.27 | 0.020 | 0.23 | 0.5 | 0.3 | 0.27 | 0.23 | 10 | 9 |
| Fenoprofen | 3.4 | 23 | 41 | 100 | 5.9 | 24 | 12 | 1.7 | 4.3 | 1.0 | 26 | 18 |
| Flufenamate | 3.0 | 80 | 9.3 | 79 | n.d. | n.d. | 3.1 | n.d. | 1.0 | n.d. | 13 | n.d. |
| Flubiprofen | 0.075 | 1.0 | 5.5 | 24 | 0.77 | 51 | 73 | 10 | 24 | 51 | 31 | 27 |
| Ibuprofen | 7.6 | 58 | 7.2 | 67 | 20 | 150 | 0.9 | 2.6 | 1.2 | 2.6 | 14 | 20 |
| Indomethacin | 0.013 | 0.46 | 1.0 | 5.0 | 0.13 | 2.0 | 80 | 10 | 11 | 4.3 | 29 | 24 |
| Ketoprofen | 0.047 | 1.0 | 2.9 | 22 | 0.24 | 6.0 | 61 | 5.1 | 22 | 6.0 | 31 | 25 |
| Ketorolac | 0.00019 | 0.0034 | 0.086 | 4.0 | 0.075 | 1.0 | 453 | 395 | 1176 | 294 | 33 | 28 |
| Meclofenamate | 0.22 | 3.0 | 0.7 | 8.0 | 0.2 | 1.0 | 3.2 | 0.91 | 2.7 | 0.3 | 22 | 11 |
| Mefenamic acid | 25 | >100 | 2.9 | >100 | 1.3 | >100 | 0.11 | 0.049 | - | - | - | - |
| Naproxen | 9.3 | 110 | 28 | 260 | 35 | 330 | 3.0 | 3.8 | 2.4 | 3.0 | 18 | 22 |
| Niflumic acid | 25 | 77 | 5.4 | 35 | 11 | 74 | 0.22 | 0.43 | 0.45 | 1.0 | 12 | 16 |
| Piroxicam | 2.4 | 15 | 7.9 | 31 | 0.17 | 7.0 | 3.3 | 0.1 | 2.1 | 0.47 | 17 | 13 |
| Sulindac sulphide | 1.9 | 38 | 55 | 100 | 1.21 | 11 | 29 | 0.64 | 2.6 | 0.29 | 20 | 10 |
| Suprofen | 1.1 | 3.0 | 8.7 | 56 | 8.3 | 100 | 7.7 | 7.3 | 19 | 33 | 30 | 26 |
| Tenidap | 0.081 | 5.0 | 2.9 | 13 | n.d. | n.d. | 35.2 | n.d. | 2.6 | n.d. | 21 | n.d. |
| Tolmetin | 0.35 | 5.0 | 0.82 | 43 | 1.3 | 13 | 2.3 | 3.8 | 8.6 | 2.6 | 28 | 21 |
| Tomoxiprol | 7.6 | 35 | 20 | 84 | 0.32 | 13 | 2.7 | 0.042 | 2.4 | 0.37 | 19 | 12 |
| Zomepirac | 0.43 | 2.0 | 0.81 | 6.0 | 0.096 | 2.0 | 1.9 | 0.22 | 3.0 | 1.0 | 23 | 17 |
| Celexocib | 1.2 | 28 | 0.83 | 6.0 | 0.34 | 3.0 | 0.7 | 0.3 | 0.21 | 0.11 | 8 | 7 |
| Etodolac | 12 | 69 | 2.2 | 8.0 | 0.94 | 3.0 | 0.2 | 0.1 | 0.12 | 0.043 | 6 | 5 |
| Meloxicam | 5.7 | 22 | 2.1 | 7 | 0.23 | 2.0 | 0.37 | 0.040 | 0.32 | 0.091 | 11 | 6 |
| Nimesulide | 10 | 41 | 1.9 | 7.0 | 0.39 | 7.0 | 0.19 | 0.038 | 0.17 | 0.17 | 7 | 8 |
| Diisopropyl fluorophosphate | >100 | >100 | 0.76 | 4.0 | 0.17 | 5.0 | <0.01 | <0.01 | <0.01 | <0.01 | 1= | 1= |
| L745,337 | >100 | >100 | 8.6 | 41 | 1.3 | 17 | <0.01 | <0.01 | <0.01 | <0.01 | 1= | 1= |
| NS398 | 6.9 | 65 | 0.35 | 1.0 | 0.042 | 1.0 | 0.051 | 0.0061 | 0.015 | 0.015 | 5 | 4 |
| Rofecoxib | 63 | >100 | 0.84 | 6.0 | 0.31 | 5.0 | 0.013 | 0.0049 | <0.05 | <0.05 | 4 | 3 |
| SC58125 | >100 | >100 | 2.0 | 10 | n.d. | n.d. | >0.01 | n.d. | <0.01 | n.d. | 1= | n.d. |
| 5-Aminosalicylic acid | 410 | >1000 | 61 | >1000 | n.d. | n.d. | 0.15 | n.d. | - | n..d. | - | n.d. |
| Ampyrone | 55 | 270 | 203 | 1000 | 85 | 670 | 3.7 | 1.5 | 3.7 | 2.5 | 24 | 19 |
| Diflunisal | 113 | 530 | 8.2 | 140 | 134 | 400 | 0.1 | 1.2 | 0.26 | 0.75 | 9 | 14 |
| Nabumetone | 460 | >1000 | >1000 | >1000 | 290 | >1000 | - | - | - | - | - | - |
| Paracetamol | >100 | >100 | 49 | >100 | 64 | >100 | - | - | - | - | - | - |
| Resveratrol | 30 | >100 | 39 | >100 | n.d. | n.d. | 1.3 | n.d. | - | - | - | n.d. |
| Salicin | >100 | >100 | >100 | >100 | n.d. | n.d. | - | n.d. | - | - | - | n.d. |
| Salicylaldehyde | >100 | >100 | >100 | >100 | n.d. | n.d. | - | n.d. | - | - | - | n.d. |
| Sodium salicylate | 4956 | 49000 | 34440 | 101000 | 482 | 45000 | 6.9 | 0.10 | 2.1 | 0.92 | 16 | 15 |
| Sulfasalazine | 3242 | 6400 | 2507 | 8300 | n.d. | n.d. | 0.8 | n.d. | 1.3 | n.d. | 15 | n.d. |
| Sulindac | >100 | >100 | >100 | >100 | 58 | >100 | - | - | - | - | - | - |
| Tamoxifen | 15 | >100 | 95 | >100 | n.d. | n.d. | 6.4 | n.d. | - | - | - | n.d. |
| Ticlopidine | 52 | >100 | 47 | >100 | n.d. | n.d. | 0.9 | n.d. | - | - | - | n.d. |
| Valeryl salicylate | 42 | >100 | 2.3 | >100 | n.d. | n.d. | 0.053 | n.d. | - | n.d. | - | n.d. |
Data is presented in the following column order: alphabetical listing of agents after division into four main groups: (top) compounds that can produce full inhibition of both COX-1 and COX-2 with poor COX-2 selectivity; (second) compounds that can produce full inhibition of COX-1 and COX-2 with >5× preference towards inhibiting COX-2 (WHMA/COX-1 < 0.2); (third) compounds that appear to be only weak inhibitors of COX-1 and COX-2. Shown are potencies (micromolar IC50 and IC80 values) of compounds against COX-1, WBA-COX-2, and WHMA-COX-2. Selectivities of compounds towards COX-1 were determined as IC50 and IC80 ratios for both WBA-COX-2/COX-1 and WHMA-COX-2/COX-1. Ranking of compounds as inhibitors of COX-2 relative to COX-1 are based on ordering of IC80 ratios; higher ranking numbers are associated with increased selectivity towards COX-1. n.d., not done.