Inhibitor sensitivity of PGHS-2, ASA-acetylated PGHS-2, and PGHS-2(S516M)
| Compound | IC50 | ||
|---|---|---|---|
| PGHS-2 (PGE2) | ASA-PGHS-2 (15-(R)-HETE) | PGHS-2(S516M) (15-(R)-HETE) | |
| μm | |||
| L-745,337 | 0.6 | 1.0 | 2.7 |
| SC-57666 | 0.01 | 0.03 | 0.06 |
| NS-398 | 0.08 | 0.1 | 0.6 |
| DuP697 | 0.01 | 0.005 | 0.01 |
| Flurbiprofen | 0.01 | 0.06 | 0.2 |
| Ketoprofen | 0.03 | 0.6 | 0.5 |
| Sulindac sulfide | 0.1 | 0.12 | 1.9 |
| Indomethacin | 3.0 | 1.5 | 1.6 |
| Meclofenamic acid | 0.05 | >240 | >240 |
| Diclofenac | 0.07 | >240 | >240 |
Microsomes containing the indicated PGHS-2 form were preincubated with varying concentrations of inhibitor for 15 min followed by the initiation of the reaction with either 2 or 10 μmarachidonic acid, for PGHS-2 or ASA-PGHS-2 and PGHS-2(S516M), respectively. IC50 values for the inhibition of PGE2 or 15(R)-HETE formation were determined by a 4-parameter logistic fit of 8-point titrations of the indicated inhibitor. Each value is an average of at least two determinations. The first four compounds are selective PGHS-2 inhibitors.