U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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=CC(=CC=C1CN2CC(C2)C(O)=O)C(\C)=N\OCC3=CC=C(C4CCCCC4)C(=C3)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
Molecular Formula C29H35F3N2O3
Molecular Weight 516.595
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description

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.

CNS Activity

Originator

Novartis
173
Curator's Comment: # Novartis Pharma AG

Approval Year

2019
334
Targets

Targets

Primary TargetPharmacologyConditionPotency
Agonist
2678
 0.39 nM [EC50]
Agonist
2678
 0.98 nM [EC50]
Agonist
2678
 750.0 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Phase III
656
SIPONIMOD

Approved Use

Unknown
Palliative
Phase II
1132
SIPONIMOD

Approved Use

Unknown
Palliative
Phase II
1132
SIPONIMOD

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
30.4 ng/mL
EXPERIMENT
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
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
EXPERIMENT
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
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
EXPERIMENT
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
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:
https://pubmed.ncbi.nlm.nih.gov/31926605
healthy, 18-50 years
n = 17
Health Status: healthy
Age Group: 18-50 years
Population Size: 17
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
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:
https://pubmed.ncbi.nlm.nih.gov/31926605
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Disc. AE: Headache, Transaminases increased...
AEs leading to
discontinuation/dose reduction:
Headache (0.1%)
Transaminases increased (0.9%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
Disc. AE: Hypertension...
AEs leading to
discontinuation/dose reduction:
Hypertension (10%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
Other AEs: Headache, Dizziness...
Other AEs:
Headache (20.8%)
Dizziness (5.7%)
Nausea (4.2%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
75 mg single, oral
Highest studied dose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
Other AEs: Headache, Dizziness...
Other AEs:
Headache (32%)
Dizziness (12.1%)
Nausea (5.5%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
10 mg 1 times / day multiple, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, adult
n = 50
Health Status: unhealthy
Age Group: adult
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
AEs

AEs

AESignificanceDosePopulation
Blurred vision 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
healthy, 18-50 years
n = 17
Health Status: healthy
Age Group: 18-50 years
Population Size: 17
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
Dizziness 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
healthy, 18-50 years
n = 17
Health Status: healthy
Age Group: 18-50 years
Population Size: 17
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
Dry lips 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
healthy, 18-50 years
n = 17
Health Status: healthy
Age Group: 18-50 years
Population Size: 17
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
Feeling hot 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
healthy, 18-50 years
n = 17
Health Status: healthy
Age Group: 18-50 years
Population Size: 17
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
Headache 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
healthy, 18-50 years
n = 17
Health Status: healthy
Age Group: 18-50 years
Population Size: 17
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
Nasopharyngitis 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
healthy, 18-50 years
n = 17
Health Status: healthy
Age Group: 18-50 years
Population Size: 17
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
Presyncope 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
healthy, 18-50 years
n = 17
Health Status: healthy
Age Group: 18-50 years
Population Size: 17
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
Vaginal discharge 5.9%
1 mg single, intravenous
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
healthy, 18-50 years
n = 17
Health Status: healthy
Age Group: 18-50 years
Population Size: 17
Sources:
https://pubmed.ncbi.nlm.nih.gov/31926605
Headache 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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Transaminases increased 0.9%
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209884s000lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, 49.0 years
n = 1148
Health Status: unhealthy
Condition: secondary progressive multiple sclerosis
Age Group: 49.0 years
Sex: M+F
Population Size: 1148
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
Dizziness 12.1%
75 mg single, oral
Highest studied dose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
Headache 32%
75 mg single, oral
Highest studied dose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
Nausea 5.5%
75 mg single, oral
Highest studied dose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 38
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, adult
n = 50
Health Status: unhealthy
Age Group: adult
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, adult
n = 50
Health Status: unhealthy
Age Group: adult
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, adult
n = 50
Health Status: unhealthy
Age Group: adult
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, adult
n = 50
Health Status: unhealthy
Age Group: adult
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, adult
n = 50
Health Status: unhealthy
Age Group: adult
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, adult
n = 50
Health Status: unhealthy
Age Group: adult
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, adult
n = 50
Health Status: unhealthy
Age Group: adult
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
unhealthy, adult
n = 50
Health Status: unhealthy
Age Group: adult
Population Size: 50
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000MedR.pdf
Page: p. 109
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

inhibitor
1587

inducer
781
substrate
1037

inhibitor
1767

inducer
389
inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1524

CYP2A6
707

CYP2C8
911

CYP2C19
1478

CYP2E1
882

BCRP
699

P-gp
1461

BSEP
402

MRP2
383

OAT1
599

OAT3
642

OCT1
512

OCT2
647

MATE1
306

MATE2
263
P-gp
1537

BCRP
561

MRP2
205
CYP1A2
701

CYP2B6
547
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
1553
 unlikely [IC50 >100 uM]
CYP2E1
970
 unlikely [IC50 >100 uM]
CYP1A2
1692
 unlikely [IC50 >200 uM]
CYP2A6
739
 unlikely [IC50 >200 uM]
CYP2C8
965
 unlikely [IC50 >200 uM]
CYP2D6
1891
 unlikely [IC50 >200 uM]
BCRP
773
 unlikely
BSEP
403
 unlikely
CYP1A2
1692
 unlikely
CYP2B6
1001
 unlikely
CYP2C9
1819
 unlikely
CYP3A4
1925
 unlikely
MATE1
308
 unlikely
MATE2
263
 unlikely
MRP2
475
 unlikely
OAT1
603
 unlikely
OAT3
644
 unlikely
OCT1
543
 unlikely
OCT2
648
 unlikely
P-gp
1650
 unlikely
CYP3A4
1925
 weak [IC50 100 uM]
CYP2C9
1819
 weak [IC50 230 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
BCRP
561
 no
MRP2
205
 no
P-gp
1537
 no
CYP3A4
1737
 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
CYP2C9
1037
 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
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
Excenen
EX-A873
Molcore
MC445558
Toronto Research Chemicals
S683660
ZINC
ZINC000138611691
http://zinc15.docking.org/substances/ZINC000138611691
mcule
MCULE-4593242052
PubMed

PubMed

TitleDatePubMed
The clinically-tested S1P receptor agonists, FTY720 and BAF312, demonstrate subtype-specific bradycardia (S1P₁) and hypertension (S1P₃) in rat.
2012
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
2012 Nov
Circulating monocytes are reduced by sphingosine-1-phosphate receptor modulators independently of S1P3.
2013 Apr 1
Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator.
2013 Mar 14
Siponimod (BAF312) prevents synaptic neurodegeneration in experimental multiple sclerosis.
2016 Aug 26
Patents

Patents

JP4700616B2
3
WO2008000419
3

Sample Use Guides

In Vivo Use Guide
Patients received 2 mg once daily siponimod (following initial dose titration starting at 0.25 mg).
Route of Administration: Oral
In Vitro Use Guide
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).
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:37:15 UTC 2023
Edited
by admin
on Sat Dec 16 01:37:15 UTC 2023
Record UNII
RR6P8L282I
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Siponimod
INN   WHO-DD  
USAN   INN  
Official Name English
1-[[4-[(1E)-1-[[[4-Cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]imino]ethyl]-2-ethylphenyl]methyl]-3-azetidinecarboxylic acid
Systematic 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 Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
FDA ORPHAN DRUG 413413
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
NCI_THESAURUS C308
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
EU-Orphan Drug EU/3/14/1370
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
Code System Code Type Description
DAILYMED
RR6P8L282I
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
LACTMED
Siponimod
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
INN
9491
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
RXCUI
2121085
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
USAN
FG-55
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
WIKIPEDIA
Siponimod
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
CAS
1230487-00-9
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
SMS_ID
100000163287
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
MERCK INDEX
m12146
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
PUBCHEM
44599207
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
EPA CompTox
DTXSID40153847
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
EVMPD
SUB177510
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
DRUG CENTRAL
5326
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
DRUG BANK
DB12371
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
NCI_THESAURUS
C152368
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
ChEMBL
CHEMBL2336071
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
FDA UNII
RR6P8L282I
Created by admin on Sat Dec 16 01:37:15 UTC 2023 , Edited by admin on Sat Dec 16 01:37:15 UTC 2023
PRIMARY
Related Record Type Details
SPHINGOSINE 1-PHOSPHATE RECEPTOR 5
TARGET -> AGONIST
Blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. Initial receptor activation is paradoxically followed by S1P1 functional antagonism, whereby receptors are internalized and degraded, thus reducing or eliminating them from the lymphocyte cell surface.40,60,70,74,75 This down-regulation renders lymphocytes unresponsive to the normal S1P gradient and thus deprives them of the obligatory signal that would ordinarily allow them to egress from lymphoid tissues and recirculate to the periphery.
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
MINOR
Structure of Siponimod
CUMULATIVE EXCRETION
FECAL
Structure of Siponimod
CUMULATIVE EXCRETION
URINE
SPHINGOSINE 1-PHOSPHATE RECEPTOR 1
TARGET -> AGONIST
Blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood.
EC50
Structure of Siponimod
EXCRETED UNCHANGED
FECAL
Structure of SIPONIMOD ADIPIC ACID
SALT/SOLVATE -> PARENT
Structure of SIPONIMOD ADIPIC ACID
SOLVATE->ANHYDROUS
CYTOCHROME P450 2C9
METABOLIC ENZYME -> SUBSTRATE
CYP2C9 genotype had a significant effect on the exposure of siponimod, with CYP2C9 *3/*3, CYP2C9 *1/*3, and CYP2C9 *2/*3 individuals having the largest effect.
MAJOR
Structure of Siponimod Fumaric Acid
SOLVATE->ANHYDROUS
Structure of Siponimod Fumaric Acid
SALT/SOLVATE -> PARENT
Structure of Siponimod
EXCRETED UNCHANGED
URINE
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
Related Record Type Details
Structure of 1-((2-ETHYL-4-((E)-N-((4-(3-HYDROXYCYCLOHEXYL)-3-(TRIFLUOROMETHYL)PHENYL)METHOXY)-C-METHYL-CARBONIMIDOYL)PHENYL)METHYL)AZETIDINE-3-CARBOXYLIC ACID
METABOLITE -> PARENT
PLASMA
Structure of 1-((4-ACETYL-2-ETHYL-PHENYL)METHYL)AZETIDINE-3-CARBOXYLIC ACID
METABOLITE -> PARENT
MINOR
FECAL; URINE
Structure of CHOLESTERYL SIPONIMOD
METABOLITE -> PARENT
Structure of DES(CYCLOHEXYL)-4-HYDROXYCYCLOHEXYL-SIPONIMOD GLUCORONIDE
METABOLITE -> PARENT
URINE
Structure of 1-((2-ETHYL-4-(1-HYDROXYETHYL)PHENYL)METHYL)AZETIDINE-3-CARBOXYLIC ACID
METABOLITE -> PARENT
MINOR
URINE
Structure of 1-((2-ETHYL-4-((E)-N-HYDROXY-C-METHYL-CARBONIMIDOYL)PHENYL)METHYL)AZETIDINE-3-CARBOXYLIC ACID
METABOLITE -> PARENT
MINOR
URINE
Structure of DES(CYCLOHEXYL)-4-HYDROXYCYCLOHEXYL-SIPONIMOD GLUCORONIDE
METABOLITE INACTIVE -> PARENT
MAJOR
PLASMA
Structure of DES(CYCLOHEXYL)-4-HYDROXYCYCLOHEXYL-SIPONIMOD
METABOLITE INACTIVE -> PARENT
MAJOR
FECAL; PLASMA; URINE
Related Record Type Details
Structure of Siponimod
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC IN HEALTHY MEN

SINGLE DOSE ADMINISTRATION

BRAIN/PLASMA RATIO PHARMACOKINETIC SPECIES
BIOLOGICAL
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966