risdiplam   Click here for help

GtoPdb Ligand ID: 11170

Synonyms: compound 1 [PMID: 30044619] | Evrysdi® | RG-7916 | RG7916 | RO-7034067 | RO7034067
Approved drug
risdiplam is an approved drug (FDA (2020), EMA (2021))
Compound class: Synthetic organic
Comment: Risdiplam is a first-in-class, orally bioavailable splicing modifier [3]. Like the splice switching oligonucleotide nusinersen, risdiplam is intended to improve the efficiency of SMN2 (HGNC ID 11118; Uniprot Q16637) gene transcription in patients with spinal muscular atrophy (SMA) [2]. Risdiplam binds directly to the SMN2 pre-mRNA to modulate its splicing pattern to produce a protein that compensates for the defective SMN1 gene.

risdiplam is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 2
Topological polar surface area 79.83
Molecular weight 401.2
XLogP 3.52
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Cc1cn2c(n1)c(C)cc(n2)c1cc(=O)n2c(n1)ccc(c2)N1CCNC2(C1)CC2
Isomeric SMILES Cc1cn2c(n1)c(C)cc(n2)c1cc(=O)n2c(n1)ccc(c2)N1CCNC2(C1)CC2
InChI InChI=1S/C22H23N7O/c1-14-9-18(26-29-11-15(2)24-21(14)29)17-10-20(30)28-12-16(3-4-19(28)25-17)27-8-7-23-22(13-27)5-6-22/h3-4,9-12,23H,5-8,13H2,1-2H3
InChI Key ASKZRYGFUPSJPN-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
The EMA granted risdiplam orphan drug designation for the treatment of SMA in 2019. Favourable efficacy and safety for risdiplam were established in the FIREFISH and SUNFISH trials. Risdiplam was FDA approved in August 2020, and EMA authorisation followed in early 2021. It is indicated for use in SMA patients ≥2 months of age.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02913482 Investigate Safety, Tolerability, PK, PD and Efficacy of Risdiplam (RO7034067) in Infants With Type1 Spinal Muscular Atrophy Phase 2/Phase 3 Interventional Hoffmann-La Roche This is the FIREFISH trial.
NCT02908685 A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Risdiplam (RO7034067) in Type 2 and 3 Spinal Muscular Atrophy (SMA) Participants Phase 2/Phase 3 Interventional Hoffmann-La Roche This is the SUNFISH trial.