TABLE 1.
Potency of Inhibitors in differentiating cultures of FSHD1 and FHD2 muscle cells
| Inhibitor | Mechanism/Selectivity | FSHD1 EC50 | FSHD2 EC50 | Clinical Advancement |
|---|---|---|---|---|
| nM | nM | |||
| Acumapimod (BCT197) | p38α/β | 13 | 6.3 | Phase II, active |
| ARRY-614 (Pexmetinib) | p38/Tie2 | 0.33 | 0.18 | Phase I, discontinued |
| BMS-582949 | p38α, 5× selective over p38β | 17 | 4.2 | Phase II, discontinued |
| Doramapimod (BIRB796) | p38α/β/γ/δ | 0.83 | 4.6 | Phase II, discontinued |
| Losmapimod (GW856553) | p38α/β | 14 | 2.4 | Phase III, discontinued |
| Neflamapimod (VX-745) | p38α, 22X selective over p38β | 12 | 13 | PhasePhs II, active |
| Ralimetinib (LY2228820) | p38α/β JNK2, JNK3 > JNK1 | 4.0 | 1.6 | Phase II, discontinued |
| Pamapimod (RO4402257) | P38α, 34X selective over p38β | 5.5 | 2.2 | Phase II, discontinued |
| PH-797804 | p38α, 4X selective over p38β | 0.15 | 0.41 | Phase II, discontinued |
| SB202190 | p38α/β | 6.0 | 5.2 | Tool compound |
| SB203580 | p38α/β | 17 | 9.5 | Tool compound |
| TAK-715 | p38α, 28X selective over p38β | 4.4 | 12 | Phase II, discontinued |
| Talmapimod (SCIO 469) | p38α, 10X selective over p38β | 1.6 | 5.0 | Phase II, discontinued |
| VX-702 | p38α, 14X selective over p38β | 4.1 | 14 | Phase II, discontinued |
| Tomivosertib (eFT-508) | MKNK1/2 (MNK1/2) | >10,000 | >10,000 | Phase II, active |
| PF-3644022 | MAPKAPK2/3 (MK2/3) | >10,000 | >10,000 | Tool compound |
| MK2-IN-1 | MAPKAPK2 (MK2) | >10,000 | >10,000 | Tool compound |