SMA Research Platform

This pipeline computationally filters thousands of ChEMBL compounds down to the best candidates for SMA drug discovery. The process runs in six steps: (1) ChEMBL query — compounds bioactive against top-scored SMA targets are fetched with their SMILES strings; (2) RDKit descriptor calculation — molecular weight, LogP, rotatable bonds, H-bond donors/acceptors, TPSA, and QED are computed from SMILES; (3) Lipinski Rule of 5— MW < 500, LogP < 5, HBD ≤ 5, HBA ≤ 10; (4) BBB permeability estimate— TPSA < 90 Ų and MW < 450; (5) CNS MPO score — 0–6 composite tuned for CNS drug development; (6) PAINS filter — substructure alerts for pan-assay interference compounds.

Why BBB penetration matters for SMA:SMA motor neurons reside in the anterior horn behind the blood-brain barrier. Risdiplam succeeds partly because of its BBB-permeable profile. Compounds with TPSA > 90 Ų or MW > 500 Da are unlikely to achieve meaningful CNS exposure.

Score glossary: Lipinski — binary pass/fail. BBB — heuristic estimate (TPSA + MW). CNS MPO — 0–6; ≥ 4 is CNS-optimized. QED — 0–1 drug-likeness; ≥ 0.5 is high quality. PAINS — substructure alert for reactive scaffolds.