SAFINAMIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H19FN2O2
Molecular Weight	302.3434
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=NEMGRZFTLSKBAP-LBPRGKRZSA-N

InChI=1S/C17H19FN2O2/c1-12(17(19)21)20-10-13-5-7-16(8-6-13)22-11-14-3-2-4-15(18)9-14/h2-9,12,20H,10-11H2,1H3,(H2,19,21)/t12-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17030736
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27536120 | http://adisinsight.springer.com/drugs/800009612

Safinamide (FCE 26743, NW 1015, PNU 151774, PNU 151774E, trade name Xadago) combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safinamide is under development with Newron, Zambon and Meiji Seika Pharma for the treatment of Parkinson's disease. Safinamide has been launched in the EU, Iceland and Liechtenstein. Safinamide was well tolerated and safe in the clinical development program that demonstrated the amelioration of motor symptoms and OFF phenomena by safinamide when combined with dopamine agonists or levodopa.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Monoamine oxidase B 72 Target ID: CHEMBL2039 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17824599	Inhibitor 8297	98.0 nM [IC50]
Sodium channel alpha subunit 76 Target ID: CHEMBL2331043 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10027853	Blocker 537	8.0 µM [IC50]
glutamate secretion 3 Target ID: GO:0014047 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10027853	Inhibitor 8297	56.4 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Parkinson's disease 226 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002396/WC500184965.pdf	Primary		Approved 8429	XADAGO Approved Use Xadago (safinamide) is indicated for the treatment of adult patients with idiopathic Parkinson’s disease (PD) as add-on therapy to a stable dose of Levodopa (L-dopa) alone or in combination with other PD medicinal products in mid-to late-stage fluctuating patients. Launch Date 2015

C_max

Value	Dose	Co-administered	Analyte	Population
650 ng/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/xadago-epar-public-assessment-report_en.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		SAFINAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
19000 ng × h/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/xadago-epar-public-assessment-report_en.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		SAFINAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
26 h OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/xadago-epar-public-assessment-report_en.pdf	single, intravenous		SAFINAMIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
11.5% OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/xadago-epar-public-assessment-report_en.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		SAFINAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg 1 times / day single, oral Highest studied dose Dose: 400 mg, 1 times / day Route: oral Route: single Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24136086/	healthy, mean age 28.7 years n = 6 Health Status: healthy Age Group: mean age 28.7 years Sex: M Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/24136086/	Other AEs: Headache... Other AEs: Headache (grade 1, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/24136086/
350 mg 1 times / day multiple, oral Higher than recommended Dose: 350 mg, 1 times / day Route: oral Route: multiple Dose: 350 mg, 1 times / day Co-administed with:: tyramine(100 to 700 mg; 7 days) Sources: https://pubmed.ncbi.nlm.nih.gov/22948897/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf	healthy, mean age 41.2 years n = 18 Health Status: healthy Age Group: mean age 41.2 years Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/22948897/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf	Disc. AE: ALT increased... Other AEs: Palpitations, Nausea... AEs leading to discontinuation/dose reduction: ALT increased (5.5%) Other AEs: Palpitations (5.5%) Nausea (5.5%) Pharyngitis (5.5%) Headache (5.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/22948897/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf
350 mg 1 times / day multiple, oral Higher than recommended Dose: 350 mg, 1 times / day Route: oral Route: multiple Dose: 350 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22948897/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf	healthy, mean age 41.2 years n = 18 Health Status: healthy Age Group: mean age 41.2 years Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/22948897/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf	Other AEs: Diarrhea, Headache... Other AEs: Diarrhea (5.5%) Headache (5.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/22948897/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf
350 mg 1 times / day multiple, oral Higher than recommended Dose: 350 mg, 1 times / day Route: oral Route: multiple Dose: 350 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000CrossR.pdf Page: 207145Orig1s000CrossR.pdf - p.13(14)	healthy n = 59 Health Status: healthy Population Size: 59 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000CrossR.pdf Page: 207145Orig1s000CrossR.pdf - p.13(14)	Other AEs: Headache, Dizziness... Other AEs: Headache (11.9%) Dizziness (5.1%) Nausea (3.4%) Nasopharyngitis (1.7%) Fatigue (3.4%) Vomiting (1.7%) Diarrhea (1.7%) Skin laceration (1.7%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000CrossR.pdf Page: 207145Orig1s000CrossR.pdf - p.13(14)
100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.121(153)	unhealthy n = 317 Health Status: unhealthy Condition: Parkinson’s disease Population Size: 317 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.121(153)	Disc. AE: Angina pectoris, Aortic valve incompetence... AEs leading to discontinuation/dose reduction: Angina pectoris (0.3%) Aortic valve incompetence (0.3%) Atrial flutter (0.3%) Creatine phosphokinase increased (0.3%) Vertigo (0.3%) Cataract (0.3%) Lacrimation increased (0.3%) Macular oedema (0.3%) Maculopathy (0.3%) Ocular vascular disorder (0.3%) Papilloedema (0.3%) Paraesthesia (0.3%) Pain of skin (0.3%) Rash erythematous (0.3%) Anaemia iron deficiency (0.3%) Depressed mood (0.3%) Bronchospasm (0.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.121(153)
100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.124(156)	unhealthy n = 498 Health Status: unhealthy Condition: Late/Advanced Stage Parkinson's disease Population Size: 498 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.124(156)	Disc. AE: Dyskinesia, Parkinson's disease... AEs leading to discontinuation/dose reduction: Dyskinesia (1.4%) Parkinson's disease (0.6%) Dizziness (0.2%) Paraesthesia (0.2%) Cognitive disorder (0.2%) Presyncope (0.2%) Abdominal pain (0.2%) Vomiting (0.2%) Hallucination, visual (0.6%) Hallucination (0.2%) Sleep terror (0.2%) Asthenia (0.2%) Muscle spasms (0.4%) Basal cell carcinoma (0.2%) Breast cancer (0.2%) Non-Hodgkin's lymphoma (0.2%) Arrhythmia (0.2%) Ventricular tachycardia (0.2%) Cataract subcapsular (0.2%) Vision blurred (0.2%) Change in ECG (0.2%) QT interval prolonged (0.2%) Blister (0.2%) Hyperhidrosis (0.2%) Fall (0.2%) Subdural haematoma (0.2%) Cachexia (0.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.124(156)
50 mg 1 times / day multiple, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.18(19)	unhealthy n = 1 Health Status: unhealthy Condition: Parkinson’s disease Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.18(19)	Disc. AE: Swollen tongue, Dyspnea... AEs leading to discontinuation/dose reduction: Swollen tongue Dyspnea Redness mouth Gingival swelling Rash trunk Decreased appetite Increased appetite Inner restlessness Redness of face Pruritus Hyperhidrosis Dry mouth Hoarseness Malaise Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.18(19)
50 mg 1 times / day multiple, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.124(156)	unhealthy n = 223 Health Status: unhealthy Condition: Late/Advanced Stage Parkinson's disease Population Size: 223 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.124(156)	Disc. AE: Dyskinesia, Dizziness... AEs leading to discontinuation/dose reduction: Dyskinesia (1.3%) Dizziness (0.4%) Paraesthesia (0.4%) Balance disorder (0.4%) Tremor (0.4%) Abdominal pain (0.4%) Vomiting (0.4%) Aphthous stomatitis (0.4%) Constipation (0.4%) Nausea (0.4%) Asthenia (0.4%) Chest discomfort (0.4%) Muscle rigidity (0.4%) Dyspnoea (0.9%) Pneumonitis (0.4%) Palpitations (0.4%) Urinary tract infection (0.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.124(156)
50 mg 1 times / day multiple, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.121(153)	unhealthy n = 226 Health Status: unhealthy Condition: Parkinson’s disease Population Size: 226 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.121(153)	Disc. AE: Myocardial infarction, Palpitations... AEs leading to discontinuation/dose reduction: Myocardial infarction (0.4%) Palpitations (0.4%) Ventricular tachycardia (0.4%) QT interval prolonged (0.9%) Blood glucose increased (0.4%) Vertigo (0.4%) Muscle spasms (0.4%) Tremor (0.4%) Nausea (0.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.121(153)
200 mg 1 times / day multiple, oral Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.121(153)	unhealthy n = 89 Health Status: unhealthy Condition: Parkinson’s disease Population Size: 89 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.121(153)	Disc. AE: Head titubation, Nausea... AEs leading to discontinuation/dose reduction: Head titubation (1.1%) Nausea (2.2%) Diarrhea (1.1%) GERD (1.1%) Vomiting (1.1%) Anxiety (1.1%) Nightmare (1.1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000MedR.pdf Page: 207145Orig1s000MedR.pdf - p.121(153)

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inducer 781	inhibitor 1767 inducer 389	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT2 647 OATP1B1 788 OATP1B3 706 BSEP 402 BCRP 699 P-gp 1461 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A4/5 278 CYP1A1 110 CYP1A2 1524 ALDH1 40	ALDH 6 P-gp 1537 UGT1A 7	CYP1A2 701 CYP2B6 547 UGT1A1 69 SULT2A1 4

Drug as perpetrator

Target	Modality	Activity	Metabolite
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	no [IC50 43 uM]
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1153 3
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1689 3
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1153 3
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1689 3
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1153 3
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1689 3
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1153 3
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1689 3
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1153 3
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1689 3
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1153 3
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1689 3
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1153 3
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1689 3
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1153 3
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1689 3
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1153 3
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	NW-1689 3
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no	NW-1153 3
SULT2A1 9	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
UGT1A1 254	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	yes [IC50 3.7 uM]	NW-1689 3
ALDH1 40	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	yes [IC50 35 uM]	NW-1689 3
CYP1A1 218	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	yes [IC50 47.7 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	yes
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	yes
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	yes
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	yes

Drug as victim

Target	Modality	Activity
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	minor
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	no
ALDH 6	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	yes
UGT1A 7	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207145Orig1s000PharmR.pdf#page=42 Page: 42.0

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA0038VE	https://www.aablocks.com/goods/Goods/detail?id=AA0038VE
AK Scientific, Inc. (AKSCI)	6135AA	http://www.aksci.com/item_detail.php?cat=6135AA
Aaron Chemicals	AR0039N6	http://www.aaronchem.com/133865-89-1
Aceschem	ACF023692	https://www.aceschem.com/catalog/133865-89-1.html
Achemo Scientific Limited	AC-74101	http://www.achemo.com/search/?Keyword= 133865-89-1
Achemtek	0102-020052	http://www.achemtek.com/133865-89-1
Adooq BioScience	A13294	https://www.adooq.com/safinamide.html
Alsachim	1719	http://www.alsachim.com/product-C2493-glo.bal-view.html
Ambeed	A189271	https://www.ambeed.com/products/133865-89-1.html
Annker Organics	P111001	http://www.annker.com/detailproe.php?id=10
Anward	ANW-58666	http://www.anward.com/pro_result/45117
ApexBio Technology	A3784	http://www.apexbt.com/safinamide.html
Aurora Fine Chemicals LLC	A24.076.620	http://online.aurorafinechemicals.com/info?ID=A24.076.620
Aurum Pharmatech LLC	W-5197	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5197
AvaChem Scientific	6759	https://www.avachem.com/productSearch.asp?6759
BLD Pharm	BD150732	http://www.bldpharm.com/products/133865-89-1.html
BioChemPartner	BCP12082	http://www.biochempartner.com/133865-89-1-BCP12082
BioSynth	J-506604	https://www.biosynth.com/en/products/all-products/products/J-506604.html
Boerchem	BC224413	http://www.boerchem.com/?product_37818.html
CSNpharm	CSN11880	https://www.csnpharm.com/products/safinamide.html
Chem Scene	CS-0556	http://www.chemscene.com/133865-89-1.html
ChemMol	44007195	http://www.chemmol.com/chemmol/44007195.html
ChemMol	99041292	http://www.chemmol.com/chemmol/99041292.html
Chemspace	CSSB00016989084	https://chem-space.com/CSSB00016989084
DC Chemicals	DC4134	http://www.dcchemicals.com/product_show-Safinamide.html
Excenen	EX-A2759	https://www.excenen.com/searchresultlist.php?id=133865-89-1
Hairui	HR108800	http://www.hairuichem.com/en/product/133865-89-1.html
Lab Network	LN01343308	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01343308
Matrix Scientific	198643	https://www.matrixscientific.com/198643.html
MedChem Express	HY-70057	https://www.medchemexpress.com/Safinamide.html
MuseChem	I001294	https://www.musechem.com/product/I001294.html
Renno Tech	RL01540	http://www.rennotech.com/product_show.asp?id=1789
Smolecule	S542288	http://www.smolecule.com/products/s542288
Synblock Inc	SB16691	http://www.synblock.com/product/133865-89-1.html
TCI (Tokyo Chemical Industry)	S0935	http://www.tcichemicals.com/eshop/en/us/commodity/S0935/index.html
THE BioTek	bt-281161	https://www.thebiotek.com/product/inhibitors/bt-281161
Yuhao Chemical	LL2156	http://www.chemyuhao.com/133865-89-1.html
abcr GmbH	AB506034	http://www.abcr.com/shop/en/AB506034
iChemical	EBD31483	http://www.ichemical.com/products/133865-89-1.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Future prospects for the drug treatment of epilepsy.	2001	11735615
Safinamide (Newron Pharmaceuticals).	2001 Jun	11572661
Novel anticonvulsant medications in development.	2002 Oct	12387702
Pressor response to intravenous tyramine in healthy subjects after safinamide, a novel neuroprotectant with selective, reversible monoamine oxidase B inhibition.	2003 Jul-Aug	12897643
Safinamide: FCE 26743, NW 1015, PNU 151774, PNU 151774E.	2004	15563241
Improvement of motor function in early Parkinson disease by safinamide.	2004 Aug 24	15326260
Pharmacokinetics and pharmacodynamics of safinamide, a neuroprotectant with antiparkinsonian and anticonvulsant activity.	2004 Jul	15082032
Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class.	2004 Mar 25	15027868
Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII).	2004 Sep-Oct	15570674
Voltage gated ion channels: targets for anticonvulsant drugs.	2005	15638775
Safinamide: from molecular targets to a new anti-Parkinson drug.	2006 Oct 10	17030736
Monoamine oxidase-B inhibition in the treatment of Parkinson's disease.	2007 Dec	18041937
Safinamide for the treatment of Parkinson's disease, epilepsy and restless legs syndrome.	2007 Jul	17659477
Solid-phase synthesis and insights into structure-activity relationships of safinamide analogues as potent and selective inhibitors of type B monoamine oxidase.	2007 Oct 4	17824599
An expert opinion on safinamide in Parkinson's disease.	2008 Jul	18549347
Recent advances in adjunctive therapy for epilepsy: focus on sodium channel blockers as third-generation antiepileptic drugs.	2010 Apr	20502724
Two polymorphs of safinamide, a selective and reversible inhibitor of monoamine oxidase B.	2010 Jun	20522954
Novel reversible monoamine oxidase A inhibitors: highly potent and selective 3-(1H-pyrrol-3-yl)-2-oxazolidinones.	2011 Dec 8	22017497
3-Acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoles: a new scaffold for the selective inhibition of monoamine oxidase B.	2011 Sep 22	21777011
1,3-Dialkyl-substituted tetrahydropyrimido[1,2-f]purine-2,4-diones as multiple target drugs for the potential treatment of neurodegenerative diseases.	2013 Dec 1	24139167
A novel selective LSD1/KDM1A inhibitor epigenetically blocks herpes simplex virus lytic replication and reactivation from latency.	2013 Feb 5	23386436

Patents

Sample Use Guides

In Vivo Use Guide

Treatment with Xadago (Safinamide) should be started at 50 mg per day. This daily dose may be increased to 100 mg/day on the basis of individual clinical need.

Route of Administration: Oral

In Vitro Use Guide

Safinamide (PNU-151774E) reduces sustained repetitive firing in a use-dependent manner without modifying the first action potential in hippocampal cultured neurons. The inhibition of the currents by PNU-151774E was concentration-related from 10 to 200 μM.

Name

Type

Language

SAFINAMIDE

Official Name

English

EMD-1195686

Code

English

safinamide [INN]

Common Name

English

EMD 1195686

Code

English

SAFINAMIDE [MI]

Common Name

English

SAFINAMIDE [USAN]

Common Name

English

Safinamide [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

N04BD03