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

amifampridine

Brand names: Firdapse, Ruzurgi

Mechanism

3,4-diaminopyridine. Blocks presynaptic Kv channels, prolongs action potential, enhances ACh release. Off-label NMJ symptomatic therapy in SMA.

Approved indications

LEMS

Related claims (11)

TypePredicateConfSource
drug efficacyAmifampridine treatment led to a statistically significant improvement in HFMSE (clinical trial result)59%35763114
motor functionAmifampridine Phosphate improved Hammersmith Functional Motor Scale Expanded (HFMSE) scores in ambulatory patients with SMA Type 3 (clinical trial result)59%NCT03781479_results
drug efficacyAmifampridine treatment led to statistically significant improvement in HFMSE compared to placebo in ambulatory SMA Type 3 patients (clinical trial result).56%PMID:35763114
safetyTransient paresthesia occurred in 33.3% of amifampridine-treated patients as the only amifampridine-related adverse event (clinical trial result).56%PMID:35763114
drug efficacyAmifampridine was effective in treating ambulatory SMA type 3 patients (clinical trial result)53%35763114
safetyAmifampridine Phosphate was associated with adverse events in ambulatory patients with SMA Type 3 (clinical trial result)53%NCT03781479_results
drug efficacyAmifampridine Phosphate demonstrated efficacy in ambulatory patients with SMA Type 3 (clinical trial result)53%NCT03781479_results
safetyNo serious adverse events were reported with amifampridine in ambulatory SMA Type 3 patients (clinical trial result).50%PMID:35763114
drug efficacyAmifampridine did not show statistically significant improvement in secondary outcomes (timed tests and quality of life) in ambulatory SMA Type 3 patients (clinical trial result).50%PMID:35763114
safetyAmifampridine was safe in treating ambulatory SMA type 3 patients (clinical trial result)45%35763114
protein interactionAmifampridine prolongs presynaptic NMJ terminal depolarization, enhancing neuromuscular transmission (mechanism of action).42%PMID:35763114

Off-Target Findings (204)

T1: 5T3: 191T4: 8
TargetRoleTierBoltz-2 iPTMChai-1 iPTMVerdict
PAK4kinaseSMAT10.952Primary SMA hit
STMN1SMAT10.721Primary SMA hit
CHRNGion_channelSMAT10.458Primary SMA hit
GAP43SMAT10.428Primary SMA hit
NCALDSMAT10.404Primary SMA hit
PTK6kinaseOFF-TARGETT30.987Selectivity flag (off-target substrate)
PRKXkinaseOFF-TARGETT30.984Selectivity flag (off-target substrate)
BTKkinaseOFF-TARGETT30.983Selectivity flag (off-target substrate)
MAPK10kinaseOFF-TARGETT30.982Selectivity flag (off-target substrate)
TGFBR1kinaseSMAT30.979Selectivity flag (off-target substrate)
CDK5kinaseOFF-TARGETT30.978Selectivity flag (off-target substrate)
PDPK1kinaseOFF-TARGETT30.977Selectivity flag (off-target substrate)
RIPK2kinaseOFF-TARGETT30.976Selectivity flag (off-target substrate)
TECkinaseOFF-TARGETT30.975Selectivity flag (off-target substrate)
AURKCkinaseOFF-TARGETT30.974Selectivity flag (off-target substrate)
GRK5kinaseOFF-TARGETT30.972Selectivity flag (off-target substrate)
IKBKBkinaseOFF-TARGETT30.972Selectivity flag (off-target substrate)
GRK1kinaseOFF-TARGETT30.970Selectivity flag (off-target substrate)
CSKkinaseOFF-TARGETT30.969Selectivity flag (off-target substrate)
PRKG1kinaseOFF-TARGETT30.969Selectivity flag (off-target substrate)
ITKkinaseOFF-TARGETT30.968Selectivity flag (off-target substrate)
CDKL1kinaseOFF-TARGETT30.967Selectivity flag (off-target substrate)
HTR5AgpcrOFF-TARGETT30.964Selectivity flag (off-target substrate)
CHUKkinaseOFF-TARGETT30.964Selectivity flag (off-target substrate)
CDK7kinaseOFF-TARGETT30.964Selectivity flag (off-target substrate)
BRAFkinaseOFF-TARGETT30.963Selectivity flag (off-target substrate)
CAMK1DkinaseOFF-TARGETT30.962Selectivity flag (off-target substrate)
PAK2kinaseOFF-TARGETT30.961Selectivity flag (off-target substrate)
HRH2gpcrOFF-TARGETT30.961Selectivity flag (off-target substrate)
NEK3kinaseOFF-TARGETT30.960Selectivity flag (off-target substrate)
AMHR2kinaseOFF-TARGETT30.960Selectivity flag (off-target substrate)
FGFR4kinaseOFF-TARGETT30.959Selectivity flag (off-target substrate)
CSNK1DkinaseOFF-TARGETT30.959Selectivity flag (off-target substrate)
MARK4kinaseOFF-TARGETT30.959Selectivity flag (off-target substrate)
DRD3gpcrOFF-TARGETT30.958Selectivity flag (off-target substrate)
MAP3K11kinaseOFF-TARGETT30.957Selectivity flag (off-target substrate)
FLT3kinaseOFF-TARGETT30.956Selectivity flag (off-target substrate)
CHRM5gpcrOFF-TARGETT30.953Selectivity flag (off-target substrate)
MAST4kinaseOFF-TARGETT30.952Selectivity flag (off-target substrate)
PTK2kinaseOFF-TARGETT30.952Selectivity flag (off-target substrate)
MAST3kinaseOFF-TARGETT30.952Selectivity flag (off-target substrate)
ADRA1DgpcrOFF-TARGETT30.951Selectivity flag (off-target substrate)
STK4kinaseOFF-TARGETT30.951Selectivity flag (off-target substrate)
ADRA2CgpcrOFF-TARGETT30.950Selectivity flag (off-target substrate)
ADRA2BgpcrOFF-TARGETT30.949Selectivity flag (off-target substrate)
MAPK6kinaseOFF-TARGETT30.949Selectivity flag (off-target substrate)
AAK1kinaseOFF-TARGETT30.949Selectivity flag (off-target substrate)
HRH4gpcrOFF-TARGETT30.948Selectivity flag (off-target substrate)
ARAFkinaseOFF-TARGETT30.947Selectivity flag (off-target substrate)
MAPK7kinaseOFF-TARGETT30.947Selectivity flag (off-target substrate)

Showing top 50 of 204 targets.

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