Details of the Drug

General Information of Drug (ID: DMVCMUJ)

Drug Name
Siponimod
Synonyms
Siponimod; Siponimod [INN]; Siponimod [WHO-DD]; BAF-312; BAF312; BAF312 (Siponimod); RR6P8L282I; 1-[[4-[(E)-N-[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]-C-methylcarbonimidoyl]-2-ethylphenyl]methyl]azetidine-3-carboxylic acid; 1230487-00-9; 3-Azetidinecarboxylic acid, 1-((4-((1E)-1-(((4-cyclohexyl-3-(trifluoromethyl)phenyl)methoxy)imino)ethyl)-2-ethylphenyl)methyl)-; CHEMBL2336071; UNII-RR6P8L282I
Indication
Disease Entry ICD 11 Status REF
Multiple sclerosis 8A40 Approved [1]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 516.6
Topological Polar Surface Area (xlogp) 4.8
Rotatable Bond Count (rotbonds) 9
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 8
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 4 h [2]
Bioavailability
The bioavailability of drug is 84% [2]
Clearance
The sytemic clearance of drug is 3.11 L/h [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 30 hours [2]
Metabolism
The drug is metabolized via the CYP2C9 enzyme [2]
Vd
The volume of distribution (Vd) of drug is 124 L [3]
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(=NOCC2=CC(=C(C=C2)C3CCCCC3)C(F)(F)F)C)CN4CC(C4)C(=O)O
InChI
KIHYPELVXPAIDH-HNSNBQBZSA-N
InChIKey
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+
Cross-matching ID
PubChem CID
44599207
CAS Number
1230487-00-9
DrugBank ID
DB12371
INTEDE ID
DR1487

Molecular Interaction Atlas of This Drug


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 Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Siponimod was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
3 An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
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 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
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15 Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
16 Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
17 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
18 Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
19 Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
20 New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
21 A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
22 A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.