discoveryMay 4, 2026
AlphaFold-3 confirms ROCK-LIMK-Cofilin therapeutic axis in SMAHeadline AlphaFold-3 batch 04.05 returned high-confidence iPTM scores (0.80-0.83) for four key protein-pair interactions previously flagged as structurally unce...
Accelerating SMA Drug Discovery Through Computational Science
We combine molecular screening, evidence analysis, and computational biology to nominate new therapeutic candidates for SMA — featuring the ROCK-LIMK2-CFL2 axis hypothesis (multi-stream computational support; pending experimental validation).
Search the Evidence Graph
Data updated 67d ago · Last: pubmed (17 items)
Flagship · Pipeline v2.4ROCK2-LIMK-CFL Kinase Axis is the SMA platform's primary therapeutic target.
Primary: ROCK2 kinase inhibition (8× drug_efficacy evidence vs LIMK2, best Vina −10.26 kcal/mol). AF3 iPTM 0.82 on ROCK2×CFL2 kinase-substrate complex, cross-validated by Boltz-2 + Chai-1. 272 MD trajectories (19 at 100ns), 5 real 100ns completions. Secondary: NMJ axis (DOK7/MuSK — monitoring). Full flagship declaration →
Computational Discovery Pipeline
Stage 0 · Generation
GenMol · MolMIM
Stage 1 · ADMET
ADMET-AI GNN · 41 endpoints
Stage 1.5 · Retrosynthesis
AiZynthFinder
Stage 2 · Safety
PAINS · hERG · CYP
Stage 3a · Rigid Dock
DiffDock v2.2 · FlowDock
Stage 3b · Induced-Fit
NeuralPLexer3
Stage 4 · Selectivity
≥5 off-target panel
Stage 5 · MD 100 ns
OpenMM · GROMACS
Stage 6 · Free Energy
MM-PBSA + FEP
Stage 7 · Orthogonal
PMIDs · scRNA
Stage 8 · Lab Handoff
ALBF · Lab-in-the-Loop
Drug Screening Funnel
25,519ChEMBL CompoundsBioactivity data
▼ 2% filtered
25,042Drug-likeness FilterLipinski + QED111,436AI-Designed MoleculesGenMol + MolMIM▼ 66% filtered
37,794DockedDiffDock v2.2▼ 99% filtered
214Positive BindersConfidence > 0▼ 94% filtered
13Dual-Target HitsHit ≥2 SMA targets0Selective LeadsLow off-target0BBB-Permeable LeadsCNS-penetrantLatest Discoveries
gpu resultApr 30, 2026
AF3 Batch 02804: LIMK2×CFL2 Substrate Interface Validates Core SMA Therapeutic Axis (iPTM=0.80)TL;DR AlphaFold-3 batch `20260429_02804` (33 protein-protein interface jobs, 5 model seeds each) ingested into the platform. First structural validation of the ...
computationApr 27, 2026
v2 validator: 3 hits PASS, methodology calibration documented3-LLM consensus validator now PRODUCTION (v2) The Spark Chai-1 saturator surfaces protein-ligand pair predictions continuously, and a Modal serverless A100 back...
announcementMay 8, 2026
FDA accepts apitegromab BLA — first muscle-targeted SMA therapy under reviewScholar Rock announced 8 May 2026 that the U.S. Food and Drug Administration has accepted its Biologics License Application (BLA) for apitegromab. The Prescript...
drug discoveryMay 8, 2026
Haloperidol — old antipsychotic shows neuroprotective effect in SMA modelsMenduti et al. (Experimental and Molecular Medicine, 2026) report that haloperidol — a D2 dopamine receptor antagonist FDA-approved since 1967 for psychosis — i...
drug discoveryMay 8, 2026
Combining splice modifiers with HDAC6 inhibition shows strong benefit in SMA modelsOsseni et al. (Brain, 2026) report that combining SMN2 splice modifiers (such as antisense oligonucleotides inducing exon 7 inclusion) with systemic HDAC6 inhib...
data updateMay 8, 2026
Salanersen — Biogen's once-yearly intrathecal ASO advances toward Phase 3What was reported At the 5th International Scientific Congress on SMA (Budapest, 11–14 March 2026), Crawford, Sansone, Hagenacker and colleagues from Biogen pre...
drug discoveryMay 8, 2026
Givinostat — DMD-approved HDAC inhibitor identified as top SMA repurposing candidateCross-database analysis of FDA-approved drugs against the HDAC6 mechanism validated by Osseni et al. (Brain 2026) for SMA identifies Givinostat (Duvyzat, Italfa...
discoveryMay 8, 2026
Cerebellar Purkinje cell pathology contributes to motor + cognitive deficits in SMAWhat was reported Gerstner, Wittig, Menedo, Ruwald, Sumner, Mentis, Pellizzoni and colleagues (Leipzig, Columbia, Johns Hopkins, Ulm, DZNE) reported at the **5t...