SMA Research Platform

Evidence graph for Spinal Muscular Atrophy

Biology-first target discovery
Christian Fischer / Bryzant Labs
13,282Targets
453Trials
84Drugs
7Datasets
42,694Sources
48,101Claims
55,096Evidence
29,646Hypotheses
DRUGapprovedsmall molecule

riluzole

Mechanism

Glutamate antagonist. Positive in SMND7 mice (2008). Only validated DiffDock hit (+0.082 at 20 poses).

Approved indications

ALS

Related claims (30)

TypePredicateConfSource
drug targetRiluzole is a glutamate inhibitor proposed as a drug target for SMA treatment.59%14623733
drug efficacyNeuroprotective drugs as olesoxime or riluzole have shown positive effects in preclinical studies but no clear efficacy in clinical trials.53%28524214
safetyRiluzole was tolerated without adverse effects or laboratory abnormalities in SMA patients.53%14623733
gene expressionRiluzole treatment decreased the relative protein expression of NF-κB in spinal cord of mice (observed in mouse model).53%37879951
drug efficacyNeuroprotective drugs as riluzole have shown positive effects in preclinical studies but no clear efficacy in clinical trials.53%28524214
drug efficacyEarly therapeutic efforts have focused on testing repurposed drugs such as phenylbutyrate (2), valproic acid (3), riluzole (6), hydroxyurea (7), and albuterol (9), none of which has demonstrated clinical effectiveness.53%W2513799405
drug efficacyRiluzole has shown some improvement in treating SMA.53%39514016
gene expressionRiluzole treatment decreased the fluorescence expression of PPIA in spinal cord of mice (observed in mouse model).53%37879951
drug efficacyEnhanced CNS biodistribution of riluzole shows promise as efficient therapeutic tool for motor neuron diseases, including amyotrophic lateral sclerosis (demonstrated in vitro and in vivo).53%40007904
motor functionRiluzole did not produce measurable improvements in motor abilities in SMA patients.53%14623733
drug efficacyRiluzole, a glutamate inhibitor, has been shown to slow the rate of decline in patients with amyotrophic lateral sclerosis, another form of motor neuron disease.53%14623733
gene expressionRiluzole treatment decreased fluorescence expression of PPIA in spinal cord of mice (observed in mouse model).53%37879951
safetyMultifunctionalized nanoparticles significantly reduce the concentration of Riluzole in non-therapeutic organs responsible of side effects (demonstrated in vivo).53%40007904
drug efficacyEdaravone, but not riluzole, was effective in rescuing motor deficits associated with cytoplasmic TDP-43 expression and, to a lesser extent, mutant TDP-43 <sup>G294V</sup> (observed in mouse model).51%40672281
neuroprotectionRiluzole treatment restored axon outgrowth caused by diminished SMN (observed in vertebrate neurons).51%W2086311610
drug efficacyEdaravone, but not riluzole, was effective in rescuing motor deficits associated with cytoplasmic TDP-43 expression and, to a lesser extent, mutant TDP-43 G294V (observed in mouse model).51%40672281
survivalSMA subjects in the riluzole treatment group showed longer survival compared to placebo group (3 of 7 treated patients alive at 30 months to 5 years versus 0 of 3 placebo patients alive at mean age 9 months).48%14623733
pathway membershipRiluzole can be activated by SK channels.47%W2086311610
drug targetThe pharmacological targets of riluzole include SK channels.47%W2086311610
drug efficacyRiluzole ameliorated the neuromuscular defects in a C. elegans SMA model and SK channel function was required for this beneficial effect (observed in mouse model).45%W2086311610
drug efficacyRiluzole extends survival by increasing the duration of symptomatic disease in the FALS model without affecting disease onset.45%9728338
neuroprotectionperipheral nerve axon puncta size is partially restored after treatment with riluzole (observed in mouse model)45%39130445
neuroprotectionRiluzole ameliorated the phenotype of the dnc-1 KD animals (observed in mouse model).45%31300701
drug efficacyMultifunctionalized nanoparticles show suitable characteristics for the release of Riluzole in the central nervous system (demonstrated in vitro and in vivo).45%40007904
drug efficacyRiluzole, which is an approved medication for ALS patients, ameliorated the phenotype of the dnc-1 KD animals (observed in C. elegans model).45%31300701
drug efficacyIt is uncertain whether riluzole has any effect in patients with SMA type I, based on the limited available evidence (clinical trial result).45%31825542
drug efficacyThe translational potential of the model was verified by predicting riluzole PK in people with spinal muscular atrophy (observed in patient cohort).45%40958536
drug efficacyRiluzole prodrugs are useful in treating spinal muscular atrophy.44%AU2022202163B2
survivalIn a small randomized controlled study, three of seven children treated with riluzole were still alive at the ages of 30, 48 and 64 months, whereas all three children in the placebo group died; but the difference was not statistically signi...41%22513939
drug targetRiluzole prodrugs are relevant for spinal muscular atrophy.36%AU2022202163B2

Off-Target Findings (246)

T1: 5T3: 224T4: 14untiered: 3
TargetRoleTierBoltz-2 iPTMChai-1 iPTMVerdict
GAP43SMAT10.824Primary SMA hit
CHRNGion_channelSMAT10.662Primary SMA hit
NCALDSMAT10.658Primary SMA hit
PFN2SMAT10.577Primary SMA hit
STMN1SMAT10.560Primary SMA hit
PTK6kinaseOFF-TARGETT30.985Selectivity flag (off-target substrate)
BTKkinaseOFF-TARGETT30.984Selectivity flag (off-target substrate)
ADORA1gpcrOFF-TARGETT30.983Selectivity flag (off-target substrate)
HTR1AgpcrOFF-TARGETT30.982Selectivity flag (off-target substrate)
FGRkinaseOFF-TARGETT30.981Selectivity flag (off-target substrate)
GRK2kinaseOFF-TARGETT30.972Selectivity flag (off-target substrate)
HTR2CgpcrOFF-TARGETT30.972Selectivity flag (off-target substrate)
FRKkinaseOFF-TARGETT30.964Selectivity flag (off-target substrate)
MAP3K3kinaseOFF-TARGETT30.964Selectivity flag (off-target substrate)
CHEK1kinaseOFF-TARGETT30.962Selectivity flag (off-target substrate)
HTR1EgpcrOFF-TARGETT30.962Selectivity flag (off-target substrate)
DRD2gpcrOFF-TARGETT30.957Selectivity flag (off-target substrate)
PTGFRgpcrOFF-TARGETT30.955Selectivity flag (off-target substrate)
EPHA1kinaseOFF-TARGETT30.955Selectivity flag (off-target substrate)
GRK1kinaseOFF-TARGETT30.952Selectivity flag (off-target substrate)
ADORA2BgpcrOFF-TARGETT30.952Selectivity flag (off-target substrate)
DRD1gpcrOFF-TARGETT30.950Selectivity flag (off-target substrate)
LGR5gpcrOFF-TARGETT30.949Selectivity flag (off-target substrate)
TGFBR1kinaseSMAT30.948Selectivity flag (off-target substrate)
LTB4R2gpcrOFF-TARGETT30.944Selectivity flag (off-target substrate)
SYKkinaseOFF-TARGETT30.942Selectivity flag (off-target substrate)
OPRD1gpcrOFF-TARGETT30.941Selectivity flag (off-target substrate)
TACR3gpcrOFF-TARGETT30.941Selectivity flag (off-target substrate)
MRGPRX1gpcrOFF-TARGETT30.940Selectivity flag (off-target substrate)
PRKCAkinaseOFF-TARGETT30.939Selectivity flag (off-target substrate)
KITkinaseOFF-TARGETT30.938Selectivity flag (off-target substrate)
EPHA5kinaseOFF-TARGETT30.938Selectivity flag (off-target substrate)
S1PR2gpcrOFF-TARGETT30.936Selectivity flag (off-target substrate)
AAK1kinaseOFF-TARGETT30.935Selectivity flag (off-target substrate)
KSR1kinaseOFF-TARGETT30.933Selectivity flag (off-target substrate)
BDKRB1gpcrOFF-TARGETT30.932Selectivity flag (off-target substrate)
ACVR2AkinaseOFF-TARGETT30.929Selectivity flag (off-target substrate)
PRKCEkinaseOFF-TARGETT30.923Selectivity flag (off-target substrate)
GIPRgpcrOFF-TARGETT30.921Selectivity flag (off-target substrate)
KISS1RgpcrOFF-TARGETT30.918Selectivity flag (off-target substrate)
SCTRgpcrOFF-TARGETT30.916Selectivity flag (off-target substrate)
MAP3K13kinaseOFF-TARGETT30.916Selectivity flag (off-target substrate)
PDPK1kinaseOFF-TARGETT30.916Selectivity flag (off-target substrate)
PAK1kinaseOFF-TARGETT30.915Selectivity flag (off-target substrate)
GPR55gpcrOFF-TARGETT30.915Selectivity flag (off-target substrate)
MINK1kinaseOFF-TARGETT30.913Selectivity flag (off-target substrate)
CCRL2gpcrOFF-TARGETT30.912Selectivity flag (off-target substrate)
CHRNB2ion_channelOFF-TARGETT30.912Selectivity flag (off-target substrate)
RIPK2kinaseOFF-TARGETT30.909Selectivity flag (off-target substrate)
PAK2kinaseOFF-TARGETT30.908Selectivity flag (off-target substrate)

Showing top 50 of 246 targets.

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