Table 1.
Ligand-binding parameters and inhibitory potency for ACE-083.
| Ligand | Surface Plasmon Resonance | Reporter-Gene Assay | ||
|---|---|---|---|---|
| ka (M−1 s−1) | kd (s−1) | KD (pM) | IC50 (pM) | |
| Activin A | 1.97 × 106 | 1.55 × 10−4 | 78.8 | 39.2 |
| Activin B | 1.93 × 107 | 1.99 × 10−4 | 10.3 | 49.2 |
| GDF8 | 5.32 × 105 | 1.85 × 10−4 | 348 | 676 |
| GDF11 | 4.77 × 106 | 7.20 × 10−5 | 15.4 | 75.9 |
ACE-083 binding to TGFβ superfamily ligands as determined by surface plasmon resonance and inhibitory potency as determined by cell-based reporter-gene assay. Data for kinetic characterization were duplicates globally fit to a 1:1 binding model with mass transfer term using BIAevaluation software. SPR assays were carried out for ACE-083 more than three times, and these data represent means of two experiments performed on separate flow cells. Inhibitory activity of ACE-083 was measured in dual-luciferase reporter assays conducted with A204 cells. IC50 values were calculated with GraphPad Prism and are the means of three independent assays, each containing duplicate samples.