Safinamide

Summary

Safinamide (CHEMBL396778) is an approved small molecule (ATC N04BD03) targeting MAOB; indicated across 4 conditions including parkinson disease and multiple system atrophy.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N04BD03
• Targets: 1 (MAOB)
• Indications: 4 conditions
• Clinical trials: 18
• Chemistry: 302.34 Da · C17H19FN2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL396778
Name	Safinamide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	131682
ATC	N04BD03
Molecular formula	C17H19FN2O2
Molecular weight	302.34
InChIKey	NEMGRZFTLSKBAP-LBPRGKRZSA-N

SMILES: C[C@@H](C(=O)N)NCC1=CC=C(C=C1)OCC2=CC(=CC=C2)F

IUPAC name: (2S)-2-[[4-[(3-fluorophenyl)methoxy]phenyl]methylamino]propanamide

Also known as: EMD 1195686, EMD-1195686, Safinamida, Safinamide, Xadago, SAFINAMIDE, safinamide, (S)-Safinamide, Sulfinamide, Safinamide; Xadago, (S)-safinamide, Safinamide Mesylate (FCE28073)

Parent form; salt/anhydrous children: CHEMBL48582

Patent coverage: 606 distinct patent families (1,454 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,274 (88%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
MAOB	Monoamine oxidase B	Inhibition	6.35	0%	P27338

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Amine oxidase [flavin-containing] A, Amine oxidase [flavin-containing] B, Amine oxidase [flavin-containing] B, Amine oxidase [flavin-containing] A, Sodium channel protein type 9 subunit alpha.

Bioactivity

ChEMBL activities: 76 potent at pChembl ≥ 5 of 86 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
MAOB	8.64	Ki	2.29	nM	CHEMBL_ACT_19049037
MAOB	8.64	Ki	2.29	nM	CHEMBL_ACT_19171950
MAOB	8.29	IC50	5.18	nM	CHEMBL_ACT_15050139
MAOB	8.29	IC50	5.18	nM	CHEMBL_ACT_19048934
MAOB	8.29	IC50	5.13	nM	CHEMBL_ACT_19049038
MAOB	8.29	IC50	5.13	nM	CHEMBL_ACT_19171877
MAOB	8.27	Ki	5.4	nM	CHEMBL_ACT_15163793
MAOB	8.22	IC50	6	nM	CHEMBL_ACT_18052418
MAOB	8.15	IC50	7	nM	CHEMBL_ACT_22798758
MAOB	8.15	IC50	7	nM	CHEMBL_ACT_24914025
MAOB	8.15	IC50	7	nM	CHEMBL_ACT_26132688
MAOB	8.12	IC50	7.67	nM	CHEMBL_ACT_13298547
MAOB	8.12	IC50	7.67	nM	CHEMBL_ACT_13845848
MAOB	8.11	IC50	7.7	nM	CHEMBL_ACT_18942262
MAOB	8.1	IC50	8	nM	CHEMBL_ACT_22792689
MAOB	8.1	IC50	8	nM	CHEMBL_ACT_26116126
MAOB	8.05	IC50	9	nM	CHEMBL_ACT_15050103
MAOB	8.05	IC50	9	nM	CHEMBL_ACT_18942343
MAOB	8.05	IC50	8.91	nM	CHEMBL_ACT_25659815
MAOB	7.85	IC50	14	nM	CHEMBL_ACT_26199616
MAOB	7.78	Ki	16.7	nM	CHEMBL_ACT_15163800
MAOB	7.77	IC50	17	nM	CHEMBL_ACT_18470303
P19643	7.75	IC50	18	nM	CHEMBL_ACT_15050138
MAOB	7.75	IC50	18	nM	CHEMBL_ACT_18936889
MAOB	7.75	IC50	18	nM	CHEMBL_ACT_24422260
MAOB	7.7	IC50	20	nM	CHEMBL_ACT_29220961
MAOB	7.68	IC50	21	nM	CHEMBL_ACT_18541974
MAOB	7.68	IC50	21	nM	CHEMBL_ACT_29247287
MAOB	7.64	IC50	23.07	nM	CHEMBL_ACT_18187137
MAOB	7.64	IC50	23	nM	CHEMBL_ACT_18771900

Target pathways

Aggregated over 1 target gene(s): MAOB.

Top Reactome pathways

5 total, by targets touching each:

Pathway	Targets	Genes
Amine Oxidase reactions	1	MAOB
Biogenic amines are oxidatively deaminated to aldehydes by MAOA and MAOB	1	MAOB
Metabolism	1	MAOB
Biological oxidations	1	MAOB
Phase I - Functionalization of compounds	1	MAOB

Dominant GO biological processes

GO term	Targets
substantia nigra development	1
dopamine catabolic process	1
hydrogen peroxide biosynthetic process	1

Indications & clinical

Indications

4 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
Parkinson disease	4	MONDO:0005180	MONDO:0005180
multiple system atrophy	2	MONDO:0007803	EFO:1001050
liver disorder	1	MONDO:0005154	EFO:0001421
kidney disorder	1	MONDO:0005240	EFO:0003086

Clinical trials

Total trials: 18.

Phase distribution

Phase	Trials
PHASE3	7
PHASE1	4
PHASE2	3
PHASE4	2
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03843944	PHASE4	COMPLETED	Overnight Switch From Rasagiline To Safinamide
NCT03968744	PHASE4	TERMINATED	Effect of Safinamide on Sleep Quality in Patients With Parkinson’s Disease
NCT00642889	PHASE3	COMPLETED	Safinamide as Add-On Therapy in Patients With Early Idiopathic Parkinson’s Disease Treated With a Stable Dose of a Single Dopamine Agonist (12 Month Extension)
NCT00643045	PHASE3	COMPLETED	Safinamide as Add-On Therapy in Patients With Early Idiopathic Parkinson’s Disease Treated With a Stable Dose of a Single Dopamine Agonist
NCT00865579	PHASE3	TERMINATED	Open-Label Trial to Determine the Long-Term Safety of Safinamide in Parkinson’s Disease Patients
NCT01028586	PHASE3	TERMINATED	MOTION, Safinamide in Early Idiopathic Parkinson’s Disease (IPD), as add-on to Dopamine Agonist (Extension of Trial 27918)
NCT01187966	PHASE3	COMPLETED	Efficacy and Safety of Safinamide (50 and 100mg/Day) Versus Placebo, in Patients With Mid-late Stage Parkinson’s Disease
NCT01286935	PHASE3	COMPLETED	18-month Study of Long-term Efficacy & Safety of Safinamide as add-on Therapy in Patients With Mid-late Stage PD
NCT03881371	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Safinamide, as add-on Therapy, in Idiopathic Chinese Parkinson’s Disease (PD) Patients With Motor Fluctuations Treated With Stable Doses of Levodopa
NCT01026428	PHASE1/PHASE2	COMPLETED	A Study to Assess the Effect of Safinamide on Levodopa Pharmacokinetics
NCT01113320	PHASE2	COMPLETED	Safinamide in Levodopa Induced Dyskinesia in Parkinson’s Disease Subjects
NCT01211587	PHASE2	COMPLETED	A Trial to Explore the Potential Benefit of Safinamide on Cognitive Impairment Associated With Parkinson’s Disease
NCT01264861	PHASE2	TERMINATED	A Study to Evaluate Safinamide’s Effect on Dopamine and Serotonin’s Availability by Using Brain Imaging
NCT01027169	PHASE1	COMPLETED	A Study to Assess the Effect of Hepatic Impairment on Safinamide Pharmacokinetics
NCT01374113	PHASE1	COMPLETED	Safinamide Renal Impairment Trial
NCT03216304	PHASE1	COMPLETED	Safinamide Steady State Interaction With Rosuvastatin
NCT03887221	PHASE1	COMPLETED	A Single and Multiple Dose Study to Assess How the Drug Enters, Moves Through and Exits the Body, Safety and Tolerability of Safinamide in Healthy Adult Chinese Volunteers
NCT03944785	Not specified	COMPLETED	Clinical Outcome Assessment of Parkinson’s Disease Patients Treated With XADAGO (Safinamide)

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

48 molecules share ≥1 primary target. Top 48 by shared-target count:

Molecule	Source	Status	Shared targets
TEDIZOLID	ChEMBL + PubChem	Phase 4 (approved)	MAOB
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	MAOB
DANTHRON	ChEMBL	Phase 4 (approved)	MAOB
DONEPEZIL	ChEMBL	Phase 4 (approved)	MAOB
FENTANYL	ChEMBL	Phase 4 (approved)	MAOB
IPRONIAZID	ChEMBL	Phase 4 (approved)	MAOB
ISTRADEFYLLINE	ChEMBL	Phase 4 (approved)	MAOB
LINEZOLID	ChEMBL	Phase 4 (approved)	MAOB
MENADIONE	ChEMBL	Phase 4 (approved)	MAOB
METHYLENE BLUE CATION	ChEMBL	Phase 4 (approved)	MAOB
MICONAZOLE	ChEMBL	Phase 4 (approved)	MAOB
MOCLOBEMIDE	ChEMBL	Phase 4 (approved)	MAOB
PARGYLINE	ChEMBL	Phase 4 (approved)	MAOB
PHENELZINE	ChEMBL	Phase 4 (approved)	MAOB
PIOGLITAZONE	ChEMBL	Phase 4 (approved)	MAOB
PRIMAQUINE	ChEMBL	Phase 4 (approved)	MAOB
RASAGILINE	ChEMBL	Phase 4 (approved)	MAOB
ROSIGLITAZONE	ChEMBL	Phase 4 (approved)	MAOB
SELEGILINE	ChEMBL	Phase 4 (approved)	MAOB
TOLOXATONE	ChEMBL	Phase 4 (approved)	MAOB
TRANYLCYPROMINE	ChEMBL	Phase 4 (approved)	MAOB
TROGLITAZONE	ChEMBL	Phase 4 (approved)	MAOB
ZONISAMIDE	ChEMBL	Phase 4 (approved)	MAOB
CURCUMIN	ChEMBL	Phase 3	MAOB
IDAZOXAN	ChEMBL	Phase 3	MAOB
QUERCETIN	ChEMBL	Phase 3	MAOB
RESVERATROL	ChEMBL	Phase 3	MAOB
ATIBEPRONE	ChEMBL	Phase 2	MAOB
BROFAROMINE	ChEMBL	Phase 2	MAOB
CIGLITAZONE	ChEMBL	Phase 2	MAOB
CLORGILINE	ChEMBL	Phase 2	MAOB
DAIDZEIN	ChEMBL	Phase 2	MAOB
FORMONONETIN	ChEMBL	Phase 2	MAOB
GENISTEIN	ChEMBL	Phase 2	MAOB
HYMECROMONE	ChEMBL	Phase 2	MAOB
LADOSTIGIL	ChEMBL	Phase 2	MAOB
LAZABEMIDE	ChEMBL	Phase 2	MAOB
LOFLUCARBAN	ChEMBL	Phase 2	MAOB
LUTEOLIN	ChEMBL	Phase 2	MAOB
MOFEGILINE	ChEMBL	Phase 2	MAOB
MOLIBRESIB	ChEMBL	Phase 2	MAOB
PHENAMAZOLINE	ChEMBL	Phase 2	MAOB
PIPERINE	ChEMBL	Phase 2	MAOB
SEMBRAGILINE	ChEMBL	Phase 2	MAOB
SUTEZOLID	ChEMBL	Phase 2	MAOB
TIOXOLONE	ChEMBL	Phase 2	MAOB
VAFIDEMSTAT	ChEMBL	Phase 2	MAOB
Medroxyprogesterone	PubChem	Approved	MAOB