Details of the Drug

General Information of Drug (ID: DM2R86O)

• Drug Name: Siponimod
• Synonyms: BAF312

Indication

Disease Entry	ICD 11	Status	REF
Multiple sclerosis	8A40	Approved	[1]
Hepatocellular carcinoma	2C12.02	Phase 3	[2]
Rheumatoid arthritis	FA20	Phase 2	[3]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 516.6
  Logarithm of the Partition Coefficient (xlogp); 4.8
  Rotatable Bond Count (rotbonds); 9
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 8
• Chemical Identifiers:
  Formula: C29H35F3N2O3
  IUPAC Name: 1-[[4-[(E)-N-[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]-C-methylcarbonimidoyl]-2-ethylphenyl]methyl]azetidine-3-carboxylic acid
  Canonical SMILES: CCC1=C(C=CC(=C1)/C(=N/OCC2=CC(=C(C=C2)C3CCCCC3)C(F)(F)F)/C)CN4CC(C4)C(=O)O
  InChI: 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+
  InChIKey: KIHYPELVXPAIDH-HNSNBQBZSA-N
• Cross-matching ID:
  PubChem CID: 44599207
  CAS Number: 1230487-00-9
  DrugBank ID: DB12371
  TTD ID: D07FKQ
  VARIDT ID: DR00743
  INTEDE ID: DR1488
  ACDINA ID: D01430
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Sphingosine-1 phosphate receptor (S1PR)	TT7BQRM	NOUNIPROTAC	Modulator	[1]
Sphingosine-1-phosphate receptor 1 (S1PR1)	TT9JZCK	S1PR1_HUMAN	Modulator	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[4]
Cytochrome P450 2C9 (CYP2C9) Main DME	DE5IED8	CP2C9_HUMAN	Substrate	[4]

Molecular Expression Atlas of This Drug

• ICD Disease Classification: 08 Nervous system disease
• Disease Class: ICD-11: 8A40 Multiple sclerosis
• The Studied Tissue: Plasmacytoid dendritic cells
• The Studied Disease: Multiple sclerosis [ICD-11:8A40]

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	9.09E-01	-9.26E-02	-3.68E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	9.85E-01	2.24E-02	7.33E-02

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Siponimod

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Siponimod and Ozanimod.	Multiple sclerosis [8A40]	[5]

Coadministration of a Drug Treating the Disease Different from Siponimod (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Siponimod and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[5]
Ivosidenib	DM8S6T7	Major	Increased risk of ventricular arrhythmias by the combination of Siponimod and Ivosidenib.	Acute myeloid leukaemia [2A60]	[5]
Oliceridine	DM6MDCF	Major	Increased risk of ventricular arrhythmias by the combination of Siponimod and Oliceridine.	Acute pain [MG31]	[5]
Levalbuterol	DM5YBO1	Moderate	Increased risk of prolong QT interval by the combination of Siponimod and Levalbuterol.	Asthma [CA23]	[6]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Siponimod caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[5]
Pexidartinib	DMS2J0Z	Major	Increased metabolism of Siponimod caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[5]
Lisocabtagene maraleucel	DMP45ME	Major	Additive immunosuppressive effects by the combination of Siponimod and Lisocabtagene maraleucel.	Diffuse large B-cell lymphoma [2A81]	[5]
Axicabtagene ciloleucel	DMYHN59	Major	Additive immunosuppressive effects by the combination of Siponimod and Axicabtagene ciloleucel.	Diffuse large B-cell lymphoma [2A81]	[5]
Eslicarbazepine	DMZREFQ	Major	Increased metabolism of Siponimod caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[5]
Bay 80-6946	DMLOS5R	Major	Additive immunosuppressive effects by the combination of Siponimod and Bay 80-6946.	Follicular lymphoma [2A80]	[5]
Avapritinib	DMK2GZX	Major	Additive immunosuppressive effects by the combination of Siponimod and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[5]
177Lu-DOTATATE	DMT8GVU	Major	Additive immunosuppressive effects by the combination of Siponimod and 177Lu-DOTATATE.	Hepatitis virus infection [1E50-1E51]	[5]
Berotralstat	DMWA2DZ	Major	Decreased metabolism of Siponimod caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[5]
Lurbinectedin	DMEFRTZ	Major	Additive immunosuppressive effects by the combination of Siponimod and Lurbinectedin.	Lung cancer [2C25]	[5]
Selpercatinib	DMZR15V	Major	Increased risk of ventricular arrhythmias by the combination of Siponimod and Selpercatinib.	Lung cancer [2C25]	[5]
Tisagenlecleucel	DMM9BJD	Major	Additive immunosuppressive effects by the combination of Siponimod and Tisagenlecleucel.	Mature B-cell lymphoma [2A85]	[5]
Belantamab mafodotin	DMBT3AI	Major	Additive immunosuppressive effects by the combination of Siponimod and Belantamab mafodotin.	Multiple myeloma [2A83]	[5]
Fedratinib	DM4ZBK6	Major	Decreased metabolism of Siponimod caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[5]
Inebilizumab	DMI0RHA	Major	Additive immunosuppressive effects by the combination of Siponimod and Inebilizumab.	Nervous system paraneoplastic/autoimmune disorder [8E4A]	[5]
Macimorelin	DMQYJIR	Major	Increased risk of ventricular arrhythmias by the combination of Siponimod and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[5]
Tildrakizumab	DMLW9HG	Major	Additive immunosuppressive effects by the combination of Siponimod and Tildrakizumab.	Psoriasis [EA90]	[5]
Risankizumab	DMM32GT	Major	Additive immunosuppressive effects by the combination of Siponimod and Risankizumab.	Psoriasis [EA90]	[5]
Upadacitinib	DM32B5U	Major	Additive immunosuppressive effects by the combination of Siponimod and Upadacitinib.	Rheumatoid arthritis [FA20]	[5]
Mogamulizumab	DMISH0Z	Major	Additive immunosuppressive effects by the combination of Siponimod and Mogamulizumab.	Sezary syndrome [2B02]	[5]
Voxelotor	DMCS6M5	Major	Decreased metabolism of Siponimod caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[5]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Siponimod caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[5]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Crospovidone	E00626	Not Available	Disintegrant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferric oxide black	E00522	16211978	Colorant
Glyceryl behenate	E00481	5362585	Binding agent; Coating agent; Flavoring agent; Modified-release agent; Viscosity-controlling agent; lubricant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Soybean lecithin	E00637	Not Available	Other agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Haematite red	E00236	14833	Colorant
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
Xanthan gum	E00694	Not Available	Bioadhesive material; Emulsifying agent; Gelling agent; Modified-release agent; Suspending agent; Viscosity-controlling agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Siponimod 0.25mg tablet	0.25mg	Tablet	Oral
Siponimod 2mg tablet	2mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [2] ClinicalTrials.gov (NCT01665144) Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND). U.S. National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Metabolism and disposition of siponimod, a novel selective S1P1/S1P5 agonist, in healthy volunteers and in vitro identification of human cytochrome P450 enzymes involved in its oxidative metabolism. Drug Metab Dispos. 2018 Jul;46(7):1001-1013.
• [5] Cerner Multum, Inc. "Australian Product Information.".
• [6] Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.