siponimod 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
immunomodulators, both stimulant/suppressive and stimulant 5326 1230487-00-9

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: 5.85
  • LIPINSKI: 1
  • HAC: 5
  • HDO: 1
  • TPSA: 62.13
  • ALOGS: -6.21
  • ROTB: 10
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
2 mg O

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class ACVR2B,EIF2AK3,GRK2,PDK1,PDK2,PDK4 6
kinase-selectivity-class AXL,EIF2AK3,GRK2 3
pfas-class PFAS structural alert (1 = True, 0 = False) 1

Approvals:

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

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
Lymphocyte count decreased 479.28 29.03 148 5529 34902 90587868
Lymphopenia 369.94 29.03 110 5567 22771 90599999
Multiple sclerosis relapse 356.91 29.03 131 5546 52174 90570596
Expanded disability status scale score increased 167.51 29.03 31 5646 792 90621978
Gait disturbance 134.69 29.03 119 5558 260377 90362393
Multiple sclerosis 129.93 29.03 53 5624 27787 90594983
Basal cell carcinoma 95.35 29.03 45 5632 33344 90589426
Balance disorder 93.01 29.03 64 5613 97016 90525754
Heart rate decreased 85.97 29.03 49 5628 53456 90569314
Headache 74.31 29.03 165 5512 862581 89760189
Urinary tract infection 64.26 29.03 87 5590 305545 90317225
White blood cell count decreased 60.79 29.03 63 5614 167046 90455724
Vision blurred 58.03 29.03 51 5626 110242 90512528
Dizziness 56.63 29.03 118 5559 589166 90033604
Leukopenia 55.87 29.03 48 5629 100662 90522108
Fall 55.33 29.03 104 5573 481706 90141064
Central nervous system lesion 53.71 29.03 22 5655 11624 90611146
Fatigue 48.52 29.03 170 5507 1153853 89468917
Feeling abnormal 41.94 29.03 52 5625 167183 90455587
COVID-19 41.54 29.03 52 5625 168791 90453979
Secondary progressive multiple sclerosis 40.94 29.03 11 5666 1568 90621202
Optic neuritis 40.30 29.03 17 5660 9661 90613109
Hemiparesis 40.27 29.03 25 5652 31794 90590976
Atrioventricular block first degree 35.61 29.03 15 5662 8496 90614274
Visual impairment 34.54 29.03 42 5635 132323 90490447
Drug titration error 33.88 29.03 9 5668 1228 90621542
Relapsing-remitting multiple sclerosis 32.65 29.03 8 5669 791 90621979
Breast cancer 32.62 29.03 27 5650 53734 90569036
Product dose omission issue 32.19 29.03 62 5615 291625 90331145
Paresis 30.92 29.03 10 5667 2704 90620066
Peroneal nerve palsy 30.45 29.03 12 5665 5736 90617034
Seizure 29.81 29.03 42 5635 152587 90470183
Muscular weakness 29.28 29.03 49 5628 206617 90416153

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 241.76 38.35 70 2427 14194 42604644
Gait spastic 141.24 38.35 29 2468 1380 42617458
Lymphopenia 139.37 38.35 51 2446 21512 42597326
Muscle spasticity 135.76 38.35 38 2459 6784 42612054
Expanded disability status scale score increased 119.22 38.35 21 2476 433 42618405
Lymphocyte count decreased 113.06 38.35 47 2450 27762 42591076
Needle fatigue 92.95 38.35 20 2477 1193 42617645
Relapsing-remitting multiple sclerosis 88.79 38.35 20 2477 1475 42617363
Multiple sclerosis 88.56 38.35 28 2469 7570 42611268
Hypertonic bladder 79.53 38.35 20 2477 2361 42616477
Monoparesis 75.21 38.35 20 2477 2940 42615898
Basal cell carcinoma 74.46 38.35 33 2464 22700 42596138
Movement disorder 70.50 38.35 28 2469 14670 42604168
Gait disturbance 68.76 38.35 52 2445 97948 42520890
Central nervous system lesion 67.49 38.35 23 2474 7847 42610991
Balance disorder 64.26 38.35 38 2459 47607 42571231
Micturition urgency 61.74 38.35 24 2473 11874 42606964
Hypoaesthesia 59.32 38.35 42 2455 71421 42547417
Urinary tract infection 57.36 38.35 47 2450 99237 42519601
Ataxia 54.69 38.35 24 2473 16101 42602737
Nocturia 47.56 38.35 20 2477 12092 42606746
Pollakiuria 47.06 38.35 24 2473 22481 42596357
Dysarthria 41.58 38.35 27 2470 39780 42579058

FDA Adverse Event Reporting System (Geriatric)

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
Lymphocyte count decreased 392.14 30.73 136 5453 57107 110526603
Multiple sclerosis relapse 319.54 30.73 113 5476 50127 110533583
Lymphopenia 292.60 30.73 100 5489 40070 110543640
Expanded disability status scale score increased 197.06 30.73 35 5554 883 110582827
Basal cell carcinoma 168.74 30.73 69 5520 45201 110538509
Gait disturbance 165.50 30.73 126 5463 278082 110305628
Multiple sclerosis 156.35 30.73 56 5533 25642 110558068
Balance disorder 129.86 30.73 78 5511 116482 110467228
Central nervous system lesion 118.11 30.73 40 5549 15513 110568197
Heart rate decreased 101.61 30.73 59 5530 82697 110501013
Relapsing-remitting multiple sclerosis 95.69 30.73 22 5567 2060 110581650
Gait spastic 85.46 30.73 19 5570 1530 110582180
Needle fatigue 83.63 30.73 18 5571 1246 110582464
Urinary tract infection 83.16 30.73 92 5497 326190 110257520
Movement disorder 82.07 30.73 39 5550 36365 110547345
Hypertonic bladder 75.29 30.73 22 5567 5280 110578430
Monoparesis 69.56 30.73 20 5569 4533 110579177
Muscle spasticity 64.62 30.73 33 5556 35882 110547828
Fall 60.88 30.73 109 5480 603373 109980337
Ataxia 58.07 30.73 29 5560 30079 110553631
Micturition urgency 53.87 30.73 24 5565 19296 110564414
Macular oedema 53.20 30.73 18 5571 6948 110576762
Fatigue 52.55 30.73 157 5432 1215801 109367909
Optic neuritis 51.99 30.73 20 5569 11127 110572583
Headache 50.07 30.73 126 5463 882251 109701459
Hypoaesthesia 49.98 30.73 70 5519 314153 110269557
Dizziness 49.72 30.73 109 5480 698084 109885626
Concomitant disease aggravated 47.79 30.73 21 5568 16343 110567367
Secondary progressive multiple sclerosis 43.35 30.73 11 5578 1558 110582152
Visual impairment 43.26 30.73 43 5546 134385 110449325
Hemiparesis 42.74 30.73 27 5562 43876 110539834
Muscular weakness 40.45 30.73 56 5533 248412 110335298
Pollakiuria 40.10 30.73 26 5563 44169 110539541
Vision blurred 39.18 30.73 40 5549 128982 110454728
Erectile dysfunction 39.13 30.73 19 5570 18537 110565173
Dysarthria 38.95 30.73 33 5556 84088 110499622
Nocturia 37.66 30.73 18 5571 16972 110566738
Atrioventricular block first degree 37.52 30.73 17 5572 14208 110569502
Memory impairment 34.48 30.73 46 5543 196898 110386812
COVID-19 33.70 30.73 51 5538 245009 110338701
Off label use 32.24 30.73 18 5571 1500167 109083543

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L04AE03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS
Sphingosine-1-phosphate (S1P) receptor modulators
MeSH PA D000081243 Sphingosine 1 Phosphate Receptor Modulators
MeSH PA D007155 Immunologic Factors
MeSH PA D007166 Immunosuppressive Agents
FDA MoA N0000181815 Sphingosine 1-Phosphate Receptor Modulators
FDA EPC N0000181816 Sphingosine 1-phosphate Receptor Modulator
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:35705 immunosuppressive agent
CHEBI has role CHEBI:231911 renoprotective agent

Related Drugs by ATC class:

L04AE Sphingosine-1-phosphate (S1P) receptor modulators 4 drugs
etrasimodfingolimodozanimodponesimod

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Secondary progressive multiple sclerosis indication 425500002 DOID:0050783
Relapsing remitting multiple sclerosis indication 426373005 DOID:2378
Sick sinus syndrome contraindication 36083008 DOID:13884
Atrioventricular block contraindication 233917008 DOID:0050820




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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
EQ 0.25MG BASE MAYZENT NOVARTIS N209884 March 26, 2019 RX TABLET ORAL 11944602 April 23, 2036 TREATMENT OF RELAPSING FORMS OF MULTIPLE SCLEROSIS (MS), TO INCLUDE CLINICALLY ISOLATED SYNDROME, RELAPSING-REMITTING DISEASE, AND ACTIVE SECONDARY PROGRESSIVE DISEASE, IN ADULTS RECEIVING OR WHO MAY RECEIVE A BETA-BLOCKER TREATMENT
EQ 0.25MG BASE MAYZENT NOVARTIS N209884 March 26, 2019 RX TABLET ORAL 12533340 April 23, 2036 TREATMENT OF RELAPSING FORMS OF MULTIPLE SCLEROSIS (MS), TO INCLUDE CLINICALLY ISOLATED SYNDROME, RELAPSING-REMITTING DISEASE, AND ACTIVE SECONDARY PROGRESSIVE DISEASE, IN ADULTS RECEIVING A BETA-BLOCKER TREATMENT
EQ 1MG BASE MAYZENT NOVARTIS N209884 Aug. 24, 2021 RX TABLET ORAL 11944602 April 23, 2036 TREATMENT OF RELAPSING FORMS OF MULTIPLE SCLEROSIS (MS), TO INCLUDE CLINICALLY ISOLATED SYNDROME, RELAPSING-REMITTING DISEASE, AND ACTIVE SECONDARY PROGRESSIVE DISEASE, IN ADULTS RECEIVING OR WHO MAY RECEIVE A BETA-BLOCKER TREATMENT
EQ 1MG BASE MAYZENT NOVARTIS N209884 Aug. 24, 2021 RX TABLET ORAL 12533340 April 23, 2036 TREATMENT OF RELAPSING FORMS OF MULTIPLE SCLEROSIS (MS), TO INCLUDE CLINICALLY ISOLATED SYNDROME, RELAPSING-REMITTING DISEASE, AND ACTIVE SECONDARY PROGRESSIVE DISEASE, IN ADULTS RECEIVING A BETA-BLOCKER TREATMENT
EQ 2MG BASE MAYZENT NOVARTIS N209884 March 26, 2019 RX TABLET ORAL 11944602 April 23, 2036 TREATMENT OF RELAPSING FORMS OF MULTIPLE SCLEROSIS (MS), TO INCLUDE CLINICALLY ISOLATED SYNDROME, RELAPSING-REMITTING DISEASE, AND ACTIVE SECONDARY PROGRESSIVE DISEASE, IN ADULTS RECEIVING OR WHO MAY RECEIVE A BETA-BLOCKER TREATMENT
EQ 2MG BASE MAYZENT NOVARTIS N209884 March 26, 2019 RX TABLET ORAL 12533340 April 23, 2036 TREATMENT OF RELAPSING FORMS OF MULTIPLE SCLEROSIS (MS), TO INCLUDE CLINICALLY ISOLATED SYNDROME, RELAPSING-REMITTING DISEASE, AND ACTIVE SECONDARY PROGRESSIVE DISEASE, IN ADULTS RECEIVING A BETA-BLOCKER TREATMENT

Orange Book exclusivity data (new drug applications)

None

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
1234627-85-0 SECONDARY_CAS_RN
4038283 VANDF
C3657824 UMLSCUI
CHEBI:754951 CHEBI
CHEMBL2336071 ChEMBL_ID
44599207 PUBCHEM_CID
DB12371 DRUGBANK_ID
CHEMBL4298150 ChEMBL_ID
D11072 KEGG_DRUG
9491 INN_ID
C578989 MESH_SUPPLEMENTAL_RECORD_UI
9289 IUPHAR_LIGAND_ID
1287380004 SNOMEDCT_US
786997005 SNOMEDCT_US
787019001 SNOMEDCT_US
J8C PDB_CHEM_ID
312581 MMSL
36617 MMSL
d09219 MMSL
017942 NDDF
017943 NDDF
2121085 RXNORM
RR6P8L282I INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
MAYZENT HUMAN PRESCRIPTION DRUG LABEL 1 0078-0979 TABLET, FILM COATED 0.25 mg ORAL NDA 30 sections
MAYZENT HUMAN PRESCRIPTION DRUG LABEL 1 0078-0986 TABLET, FILM COATED 2 mg ORAL NDA 30 sections
MAYZENT HUMAN PRESCRIPTION DRUG LABEL 1 0078-1014 TABLET, FILM COATED 1 mg ORAL NDA 30 sections