siponimod Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
5326 1230487-009

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • siponimod
  • siponimod fumaric acid
  • mayzent
  • NVP-BAF312-NX
  • BAF-312
Siponimod is a sphingosine-1-phosphate (S1P) receptor modulator. Siponimod binds with high affinity to S1P receptors 1 and 5. Siponimod blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which siponimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system.
  • Molecular weight: 516.61
  • Formula: C29H35F3N2O3
  • CLOGP: -6.21
  • LIPINSKI: 1
  • HAC: 5
  • HDO: 1
  • TPSA: 62.13
  • ALOGS: 6
  • ROTB: 10

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Jan. 13, 2020 EMA Novartis Europharm Limited
March 26, 2019 FDA NOVARTIS PHARMS CORP
June 29, 2020 PMDA Novartis Pharma K.K.

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Multiple sclerosis relapse 174.87 30.73 73 2976 44780 53301237
Lymphocyte count decreased 174.21 30.73 64 2985 27988 53318029
Lymphopenia 95.54 30.73 36 3013 16807 53329210
Multiple sclerosis 91.77 30.73 40 3009 27113 53318904
Gait disturbance 84.75 30.73 71 2978 158771 53187246
Expanded disability status scale score increased 72.49 30.73 13 3036 305 53345712
Headache 59.60 30.73 108 2941 536713 52809304
Secondary progressive multiple sclerosis 59.11 30.73 14 3035 1318 53344699
Basal cell carcinoma 52.52 30.73 26 3023 23443 53322574
Fatigue 51.65 30.73 122 2927 730384 52615633
Dizziness 43.83 30.73 77 2972 372182 52973835
Balance disorder 41.56 30.73 34 3015 73173 53272844
Product dose omission issue 40.23 30.73 52 2997 191568 53154449
Vision blurred 38.91 30.73 35 3014 85569 53260448
White blood cell count decreased 38.12 30.73 41 3008 124434 53221583
Heart rate decreased 36.53 30.73 24 3025 36923 53309094
Feeling abnormal 35.31 30.73 41 3008 135260 53210757
Visual impairment 33.50 30.73 30 3019 72882 53273135

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Multiple sclerosis relapse 101.49 37.15 29 885 11752 32500860
Multiple sclerosis 44.79 37.15 14 900 7630 32504982
Basal cell carcinoma 40.28 37.15 16 898 17552 32495060

Pharmacologic Action:

SourceCodeDescription
ATC L04AA42 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS
Selective immunosuppressants
MeSH PA D007155 Immunologic Factors
MeSH PA D007166 Immunosuppressive Agents
MeSH PA D000081243 Sphingosine 1 Phosphate Receptor Modulators

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Relapsing remitting multiple sclerosis indication 426373005 DOID:2378
Sick sinus syndrome contraindication 36083008 DOID:13884
Atrioventricular block contraindication 233917008 DOID:0050820

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.28 acidic
pKa2 7.69 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 0.25MG BASE MAYZENT NOVARTIS N209884 March 26, 2019 RX TABLET ORAL 8492441 Nov. 30, 2030 A METHOD OF TREATING MULTIPLE SCLEROSIS BY ADMINISTERING SIPONIMOD USING A TITRATION SCHEME TO REACH A MAINTENANCE DOSE
EQ 1MG BASE MAYZENT NOVARTIS N209884 Aug. 24, 2021 RX TABLET ORAL 8492441 Nov. 30, 2030 A METHOD OF TREATING MULTIPLE SCLEROSIS BY ADMINISTERING SIPONIMOD USING A TITRATION SCHEME TO REACH A MAINTENANCE DOSE
EQ 2MG BASE MAYZENT NOVARTIS N209884 March 26, 2019 RX TABLET ORAL 8492441 Nov. 30, 2030 A METHOD OF TREATING MULTIPLE SCLEROSIS BY ADMINISTERING SIPONIMOD USING A TITRATION SCHEME TO REACH A MAINTENANCE DOSE

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 0.25MG BASE MAYZENT NOVARTIS N209884 March 26, 2019 RX TABLET ORAL March 26, 2024 NEW CHEMICAL ENTITY
EQ 1MG BASE MAYZENT NOVARTIS N209884 Aug. 24, 2021 RX TABLET ORAL March 26, 2024 NEW CHEMICAL ENTITY
EQ 2MG BASE MAYZENT NOVARTIS N209884 March 26, 2019 RX TABLET ORAL March 26, 2024 NEW CHEMICAL ENTITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Sphingosine 1-phosphate receptor 1 GPCR MODULATOR EC50 9.41 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Sphingosine 1-phosphate receptor 5 GPCR MODULATOR EC50 9.01 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Sphingosine 1-phosphate receptor 4 GPCR MODULATOR EC50 6.13 SCIENTIFIC LITERATURE
Sphingosine 1-phosphate receptor 3 GPCR MODULATOR EC50 3 SCIENTIFIC LITERATURE
Sphingosine 1-phosphate receptor 2 GPCR MODULATOR EC50 4 SCIENTIFIC LITERATURE

External reference:

IDSource
RR6P8L282I UNII
4038283 VANDF
C3657824 UMLSCUI
J8C PDB_CHEM_ID
CHEMBL2336071 ChEMBL_ID
44599207 PUBCHEM_CID
DB12371 DRUGBANK_ID
CHEMBL4298150 ChEMBL_ID
D11072 KEGG_DRUG
C578989 MESH_SUPPLEMENTAL_RECORD_UI
9289 IUPHAR_LIGAND_ID
1230487-00-9 SECONDARY_CAS_RN
9491 INN_ID
2121085 RXNORM
017942 NDDF
017943 NDDF
786997005 SNOMEDCT_US
787019001 SNOMEDCT_US
312581 MMSL
36617 MMSL
d09219 MMSL

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
MAYZENT HUMAN PRESCRIPTION DRUG LABEL 1 0078-0979 TABLET, FILM COATED 0.25 mg ORAL NDA 29 sections
MAYZENT HUMAN PRESCRIPTION DRUG LABEL 1 0078-0986 TABLET, FILM COATED 2 mg ORAL NDA 29 sections