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Details

Stereochemistry ACHIRAL
Molecular Formula C29H35F3N2O3
Molecular Weight 516.595
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of Siponimod

SMILES

CCC1=C(CN2CC(C2)C(O)=O)C=CC(=C1)C(\C)=N\OCC3=CC(=C(C=C3)C4CCCCC4)C(F)(F)F

InChI

InChIKey=KIHYPELVXPAIDH-HNSNBQBZSA-N
InChI=1S/C29H35F3N2O3/c1-3-21-14-23(10-11-24(21)15-34-16-25(17-34)28(35)36)19(2)33-37-18-20-9-12-26(22-7-5-4-6-8-22)27(13-20)29(30,31)32/h9-14,22,25H,3-8,15-18H2,1-2H3,(H,35,36)/b33-19+

HIDE SMILES / InChI
Siponimod (BAF312) is a dual agonist at the sphingosine-1 phosphate receptors, S1PR1 and S1PR5. The S1P receptor is commonly found on the surface of specific cells residing in the central nervous system (CNS), that are responsible for causing CNS damage that drives loss of function in secondary progressive multiple sclerosis (SPMS). Siponimod (BAF312) enters the brain and by binding to these specific receptors, may prevent the activation of these harmful cells, helping to reduce the loss of physical and cognitive function associated with SPMS.

Originator

Curator's Comment: # Novartis Pharma AG

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.39 nM [EC50]
0.98 nM [EC50]
750.0 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
SIPONIMOD

Approved Use

Unknown
Palliative
SIPONIMOD

Approved Use

Unknown
Palliative
SIPONIMOD

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
30.4 ng/mL
2 mg 1 times / day steady-state, oral
dose: 2 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SIPONIMOD plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
558 ng × h/mL
2 mg 1 times / day steady-state, oral
dose: 2 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SIPONIMOD plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
30 h
2 mg 1 times / day steady-state, oral
dose: 2 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SIPONIMOD plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
healthy, 18-50 years
Health Status: healthy
Age Group: 18-50 years
Sources:
Other AEs: Feeling hot, Dizziness...
Other AEs:
Feeling hot (5.9%)
Dizziness (5.9%)
Headache (5.9%)
Presyncope (5.9%)
Blurred vision (5.9%)
Dry lips (5.9%)
Nasopharyngitis (5.9%)
Vaginal discharge (5.9%)
Sources:
2 mg 1 times / day steady, oral
Recommended
unhealthy, 49.0 years
Disc. AE: Headache, Transaminases increased...
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Disc. AE: Hypertension...
AEs leading to
discontinuation/dose reduction:
Hypertension (10%)
Sources:
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Disc. AE: Macular edema, ALT increased...
AEs leading to
discontinuation/dose reduction:
Macular edema (1%)
ALT increased (0.5%)
Bradycardia (0.3%)
GGT increased (0.3%)
AST increased (0.3%)
Depression (0.3%)
Dizziness (0.3%)
Fatigue (0.3%)
Pulmonary function test decreased (0.3%)
Angina pectoris (0.2%)
Edema peripheral (0.2%)
Seminoma (0.2%)
Uveitis (0.2%)
Lymphopenia (0.1%)
Urinary tract infection (0.1%)
Sources:
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
healthy, adult
Other AEs: Headache, Dizziness...
Other AEs:
Headache (20.8%)
Dizziness (5.7%)
Nausea (4.2%)
Sources:
75 mg single, oral
Highest studied dose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources:
healthy, adult
Other AEs: Headache, Dizziness...
Other AEs:
Headache (32%)
Dizziness (12.1%)
Nausea (5.5%)
Sources:
10 mg 1 times / day multiple, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Disc. AE: Macular edema, ALT increased...
AEs leading to
discontinuation/dose reduction:
Macular edema (2%)
ALT increased (2%)
ALT increased (2%)
AST increased (2%)
Dizziness (4%)
Edema peripheral (2%)
Headache (2%)
Lymphopenia (4%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Blurred vision 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
healthy, 18-50 years
Health Status: healthy
Age Group: 18-50 years
Sources:
Dizziness 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
healthy, 18-50 years
Health Status: healthy
Age Group: 18-50 years
Sources:
Dry lips 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
healthy, 18-50 years
Health Status: healthy
Age Group: 18-50 years
Sources:
Feeling hot 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
healthy, 18-50 years
Health Status: healthy
Age Group: 18-50 years
Sources:
Headache 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
healthy, 18-50 years
Health Status: healthy
Age Group: 18-50 years
Sources:
Nasopharyngitis 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
healthy, 18-50 years
Health Status: healthy
Age Group: 18-50 years
Sources:
Presyncope 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
healthy, 18-50 years
Health Status: healthy
Age Group: 18-50 years
Sources:
Vaginal discharge 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
healthy, 18-50 years
Health Status: healthy
Age Group: 18-50 years
Sources:
Headache 0.1%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
unhealthy, 49.0 years
Transaminases increased 0.9%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
unhealthy, 49.0 years
Hypertension 10%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Lymphopenia 0.1%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Urinary tract infection 0.1%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Angina pectoris 0.2%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Edema peripheral 0.2%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Seminoma 0.2%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Uveitis 0.2%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
AST increased 0.3%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Bradycardia 0.3%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Depression 0.3%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Dizziness 0.3%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Fatigue 0.3%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
GGT increased 0.3%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Pulmonary function test decreased 0.3%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
ALT increased 0.5%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Macular edema 1%
Disc. AE
2 mg 1 times / day steady, oral
Recommended
Dose: 2 mg, 1 times / day
Route: oral
Route: steady
Dose: 2 mg, 1 times / day
Sources:
unhealthy, 49.0 years
Health Status: unhealthy
Age Group: 49.0 years
Sex: M+F
Sources:
Headache 20.8%
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
healthy, adult
Nausea 4.2%
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
healthy, adult
Dizziness 5.7%
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
healthy, adult
Dizziness 12.1%
75 mg single, oral
Highest studied dose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources:
healthy, adult
Headache 32%
75 mg single, oral
Highest studied dose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources:
healthy, adult
Nausea 5.5%
75 mg single, oral
Highest studied dose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources:
healthy, adult
ALT increased 2%
Disc. AE
10 mg 1 times / day multiple, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
ALT increased 2%
Disc. AE
10 mg 1 times / day multiple, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
AST increased 2%
Disc. AE
10 mg 1 times / day multiple, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Edema peripheral 2%
Disc. AE
10 mg 1 times / day multiple, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Headache 2%
Disc. AE
10 mg 1 times / day multiple, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Macular edema 2%
Disc. AE
10 mg 1 times / day multiple, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Dizziness 4%
Disc. AE
10 mg 1 times / day multiple, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Lymphopenia 4%
Disc. AE
10 mg 1 times / day multiple, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
unlikely [IC50 >100 uM]
unlikely [IC50 >100 uM]
unlikely [IC50 >200 uM]
unlikely [IC50 >200 uM]
unlikely [IC50 >200 uM]
unlikely [IC50 >200 uM]
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
weak [IC50 100 uM]
weak [IC50 230 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
yes
yes (co-administration study)
Comment: administered with fluconazole (moderate CYP2C9 and CYP3A4 dual inhibitor): increased siponimod’s Cmax by 10% and the AUC 2-fold; administered with rifampin (strong CYP3A4 and moderate CYP2C9 dual inducer) decreased siponimod AUCtau,ss and Cmax,ss by 57% and 45%, respectively.
Page: 16.0
yes
yes (pharmacogenomic study)
Comment: administered with fluconazole (moderate CYP2C9 and CYP3A4 dual inhibitor): increased siponimod’s Cmax by 10% and the AUC 2-fold; administered with rifampin (strong CYP3A4 and moderate CYP2C9 dual inducer) decreased siponimod AUCtau,ss and Cmax,ss by 57% and 45%, respectively.
Page: 16.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
2012 Nov
Patents

Sample Use Guides

Patients received 2 mg once daily siponimod (following initial dose titration starting at 0.25 mg).
Route of Administration: Oral
The selectivity of siponimod (BAF312) for receptor subtypes S1P1 and S1P5, sparing activity on the S1P2, S1P3 and S1P4 receptors, was demonstrated by measuring agonist efficacy in the GTPγ[35S] binding assay. The half-maximal effective concentration (EC50) values were in the sub-nanomolar range for S1P1 (0.39 ± 0.07 nM) and S1P5 (0.98 ± 0.43 nM) receptors, with Emax levels of approximately 100% (full agonist).
Name Type Language
1-[[4-[(1E)-1-[[[4-Cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]imino]ethyl]-2-ethylphenyl]methyl]-3-azetidinecarboxylic acid
Preferred Name English
Siponimod
INN   WHO-DD  
USAN   INN  
Official Name English
3-Azetidinecarboxylic acid, 1-[[4-[(1E)-1-[[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]imino]ethyl]-2-ethylphenyl]methyl]-
Systematic Name English
siponimod [INN]
Common Name English
NVP-BAF312-NX
Code English
Siponimod [WHO-DD]
Common Name English
BAF312
Code English
BAF-312
Code English
SIPONIMOD [USAN]
Common Name English
SIPONIMOD [MI]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 437614
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
FDA ORPHAN DRUG 413413
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
NCI_THESAURUS C308
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
EU-Orphan Drug EU/3/14/1370
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
Code System Code Type Description
DAILYMED
RR6P8L282I
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
LACTMED
Siponimod
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
INN
9491
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
RXCUI
2121085
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
USAN
FG-55
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
WIKIPEDIA
Siponimod
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
CAS
1230487-00-9
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
SMS_ID
100000163287
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
MERCK INDEX
m12146
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
PUBCHEM
44599207
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
EPA CompTox
DTXSID40153847
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
EVMPD
SUB177510
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
DRUG CENTRAL
5326
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
DRUG BANK
DB12371
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
NCI_THESAURUS
C152368
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
ChEMBL
CHEMBL2336071
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY
FDA UNII
RR6P8L282I
Created by admin on Mon Mar 31 20:55:28 GMT 2025 , Edited by admin on Mon Mar 31 20:55:28 GMT 2025
PRIMARY