Antagonist inhibition of GDF11- or MSTN-induced ActR2b/ALK5 dimerization
Potency [IC50 and IC90 (nM) ± S.E.M.] and efficacy (percentage of inhibition) of GASP1, GASP2, and follistatin indicate their ability to block receptor dimerization. Antagonists effect on GDF11- and MSTN-induced ActR2b/ALK5 dimerization. Follistatin, and to a lesser extent GASP1, effectively blocked GDF11- and MSTN-induced ActR2b/ALK5 dimerization. GASP2 had no effect.
| ActR2b/ALK5 | IC50 | IC90 | Inhibition |
|---|---|---|---|
| nM | nM | % | |
| Follistatin_GDF11 | 0.46 ± 0.026 | 0.91 ± 0.028 | 100 |
| Follistatin_MSTN | 2.15 ± 0.081 | 4.65 ± 1.18 | 100 |
| GASP1_GDF11 | 0.37 ± 0.006 | 0.88 ± 0.029 | 80 |
| GASP1_MSTN | 1.83 ± 0.1 | 4.96 ± 0.012 | 60 |
| GASP2_GDF11 | NR | NR | NR |
| GASP2_MSTN | NR | NR | NR |
IC90, 90% inhibitory concentration; NR, no response.