nusinersen

Ligand id: 9416

Name: nusinersen

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 189
Hydrogen bond donors 27
Rotatable bonds 176
Topological polar surface area 3045.87
Molecular weight 7126.31
XLogP -31.15
No. Lipinski's rules broken 3

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Nusinersen was approved in December 2016 for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients. Phase 1 trial results are reported in [2] and Phase 2 results in [3]. Nusinersen is administered directly to the central nervous system via intrathecal injection.
Mechanism Of Action and Pharmacodynamic Effects
Nusinersen improves production of the SMN2 protein [5], whose loss causes the neuromuscular disease SMA. Nusinersen restores proper splicing of exon 7 which is abnormally slpiced-out in SMA patients. Loss of exon 7 results in a truncated SMN2 protein (SMNdelta7 protein) which is unstable and inactive, leading to reduced levels of functional SMN protein. Nusinersen-induced restoration of SMN2 protein levels provides therapeutic benefit. The molecular mechanism underlying the ability of ASOs to modulate alternative splicing was originally described in [6].