DrugBank ID:

DB15305

Description:

Risdiplam is an orally bioavailable mRNA splicing modifier used for the treatment of spinal muscular atrophy (SMA).It increases systemic SMN protein concentrations by improving the efficiency ofSMN2gene transcription. This mechanism of action is similar to its predecessornusinersen, the biggest difference being their route of administration [DrugBank]

Targets:

Spinal muscular atrophy (SMA) is a severe and progressive congenital neuromuscular disease resulting from mutations in the survival of motor neuron 1 (SMN1) gene responsible for making SMN proteins.3 Clinical features of SMA include degeneration of motor neurons in the spinal cord which ultimately leads to muscular atrophy and, in some cases, loss of physical strength.1 SMN proteins are expressed ubiquitously throughout the body and are thought to hold diverse intracellular roles in DNA repair, cell signaling, endocytosis, and autophagy.1 A secondary SMN gene (SMN2) can also produce SMN proteins, but a small nucleotide substitution in its sequence results in the exclusion of exon 7 during splicing in approximately 85% of the transcripts - this means that only ~15% of the SMN proteins produced by SMN2 are functional,1 which is insufficient to compensate for the deficits caused by SMN1 mutations. Emerging evidence suggests that many cells and tissues are selectively vulnerable to reduced SMN concentrations, making this protein a desirable target in the treatment of SMA.1 [DrugBank]

Pharmacodynamics:

Risdiplam helps to alleviate symptoms of spinal muscular atrophy by stimulating the production of a critical protein in which these patients are deficient. Early trials with risdiplam demonstrated up to a 2-fold increase in SMN protein concentration in SMA patients after 12 weeks of therapy.2 [DrugBank]

SMILES:

Cc1cn2nc(-c3cc(=O)n4cc(N5CCNC6(CC6)C5)ccc4n3)cc(C)c2n1

2D structures:  

3D structures: