announcementApr 7, 2026· SMA Research Platform
Fasudil Stage 5 PASS — Ligand Stable in ROCK2 Pocket (4.2Å, 20ns MD)
#Fasudil#ROCK2#MD#Stage5#PASS#lead_compound
⚠️ UPDATE (2026-04-17): Fasudil's original rationale (ROCK2 hyperactivation) is inverted — our meta-analysis shows ROCK2 DOWN in SMA motor neurons. Fasudil's therapeutic mechanism is now framed as muscle-mediated, not neuroprotective. Stage 5 MD stability remains valid as a structural finding; therapeutic claim is under re-derivation.
Result: PASS
Fasudil remains stably bound in the ROCK2 ATP pocket through 20ns holo MD.
Key Metrics
| Metric | Value | Gate | Verdict |
|---|---|---|---|
| Closest CA | 4.2 Å | < 10 Å | PASS |
| 5 nearest CAs | 4.2, 5.7, 5.9, 6.0, 6.4 Å | Contact | IN POCKET |
| Energy | 200 frames, 100K atoms | Stable | OK |
| Duration | 2.26h on RTX 3090 | — | — |
Why Fasudil is the Lead
- Approved drug in Japan (ROCK inhibitor)
- BBB: 0.93 (best of all tested)
- ADMET-AI: clean, no toxicity flags
- Preclinical SMA: Bowerman et al. 2012
- Mechanism: ROCK2→LIMK2→CFL2 pathway inhibition restores actin dynamics in SMA motor neurons
vs bbb5
| Fasudil | bbb5 | |
|---|---|---|
| Closest CA | 4.2 Å | >100 Å |
| Stage 5 | PASS | FAIL |
| Drug status | Approved | Novel |
Next: MMPBSA + Simon handoff package
Raw data: github.com/Bryzant-Labs/sma-research/results/md_simulations/