5 Parallel Drug Discovery Tracks — All Active

Track 1: Fasudil → Simon Handoff (READY)

• Target: ROCK2 (upstream of LIMK2)
• Result: 4.2A binding, 20ns MD stable
• Status: Approved drug (Japan 1995), BBB 0.93, Bowerman 2012 preclinical
• Next: Compound card + evidence package → Simon tests in motor neuron culture
• Timeline: Ready NOW

Track 2: PocketXMol DFG-out → Selective LIMK2 (P0)

• Target: LIMK2 allosteric pocket (DFG-out, Type III inhibitor)
• Why: ATP pocket selectivity impossible (LIMK1/LIMK2/ROCK1 identical). DFG-out differs.
• Status: 200 molecules queued on GPU fleet, P0 priority
• Reference: MDI-114215 (Fragile X LIMK, PMID 39711116) uses same approach
• Timeline: 2-3 weeks to validated selective hit

Track 3: bbb5 = Proof of Concept (COMPLETED)

• Target: LIMK2 ATP pocket
• Result: 2.4A binding at 100ns (stable!), QED 0.923, BBB 0.81
• Selectivity: NOT selective — binds LIMK1 (2.8A), ROCK1 (1.7A)
• Value: Proves AI-designed compounds bind real targets. Pipeline validation.
• Paper: "AI-designed kinase binder validated by molecular dynamics"

Track 4: 4-AP Mechanism Studies (RUNNING)

• Target: SMN2 (2.0A confirmed), Kv1.2 (running), RIPK1 (running)
• Status: 36 completed tasks. Novel RIPK1 necroptosis hypothesis.
• Note: Phase 2 clinical FAILED as Kv blocker. Mechanism study only.
• Next: MMPBSA + selectivity SMN2 vs Kv1.2 + RIPK1 binding analysis

Track 5: Riluzole (ALS Drug → SMA)

• Target: SMN2 (1.6A confirmed — TIGHTEST of all)
• Status: Approved ALS drug, now shown to bind SMN2
• Next: MMPBSA + selectivity vs glutamate receptor
• Significance: If Riluzole modulates SMN2, this is a novel repurposing angle

Compound Summary Table

293 total tasks, 6 GPUs burning, fleet autonomous.