Table 5. Relative Affinities and Selectivities of Synthetic Prostaglandins for PG Receptor Sub-Typesa.
| PG receptor
binding inhibition constants (Ki, nM) and FP receptor selectivity (x) |
||||||||
|---|---|---|---|---|---|---|---|---|
| PG analogue | DP | EP1 | EP2 | EP3 | EP4 | FP | IP | TP |
| travoprost free acid ((S)-fluprostenol) | 52 000 ± 7 200 (x 1 486) | 9 540 ± 1 240 (x 273) | nd | 3 501 ± 461 (x 100) | 41 000 ± 2 590 (x 1 171) | 35 ± 5 | ≥90 000 (x 2 571) | ≥121 000 (x 3 457) |
| (R/S)-fluprostenol free acid | >50 000 (x 510) | 12 300 ± 1 240 (x 126) | >100 000 (x 1020) | 4 533 ± 597 (x 46) | 14 400 ± 1 550 (x 147) | 98 ± 9 | >60 500 (x 617) | 121 063 ± 20 714 (x 1 235) |
| bimatoprost free acid (17-phenyl-PGF2α) | >90 000 (x 1 084) | 95 ± 27 (x 1) | nd | 387 ± 126 (x 5) | 25 700 ± 2 060 (x 310) | 83 ± 2 | >100 000 (x 1 205) | >77 000 (x 928) |
| latanoprost free acid (PHXA85) | ≥20 000 (x 204) | 2 060 ± 688 (x 21) | 39 667 ± 5 589 (x 405) | 7 519 ± 879 (x 77) | 75 000 ± 2 830 (x 765) | 98 ± 11 | ≥90 000 (x 918) | ≥60 000 (x 612) |
| bimatoprost (Amide) | >90 000 (x 14) | 19 100 ± 1 450 (x 3) | nd | >100 000 (x 16) | >100 000 (x 16) | 6 310 ± 1 650 | >100 000 (x 16) | >100 000 (x 16) |
| unoprostone (free acid) | >43 000 (x 7) | 11 700 ± 2 710 (x 2) | nd | ≥22 000 (x 4) | 15 200 ± 3 500 (x 3) | 5 900 ± 710 | >30 000 (x 5) | >30 000 (x 5) |
| natural endogenous PG ligand PGF2α | 18 000 ± 6 460 (x 138) | ±12 (x 5) | 964 ± 64 # | 24 ± 8 (x 0.2) | ±25 (x 3) | 130 ± 6 | ≥50 000 (x 385) | ≥190 000 (x 1 462) |
a
Data are mean ± SEMs from >3 experiments for each compound in each assay. The values in parentheses are the relative FP-receptor selectivities of the compounds. Note that the naturally occurring PGF2α lacks selectivity but the synthetic compounds such as travoprost free acid and latanoprost free acid exhibit significant FP-receptor selectivity.158