FINGOLIMOD LAURYL SULFATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H33NO2.C12H26O4S
Molecular Weight	573.868
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CCCCCCCCCCCCOS(O)(=O)=O.CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1

InChI

InChIKey=XTLZVNMZICNQBB-UHFFFAOYSA-N

InChI=1S/C19H33NO2.C12H26O4S/c1-2-3-4-5-6-7-8-17-9-11-18(12-10-17)13-14-19(20,15-21)16-22;1-2-3-4-5-6-7-8-9-10-11-12-16-17(13,14)15/h9-12,21-22H,2-8,13-16,20H2,1H3;2-12H2,1H3,(H,13,14,15)

HIDE SMILES / InChI

Description

Fingolimod (FTY720) is a sphingosine 1-phosphate receptor modulator indicated and approved for the treatment of relapsing-remitting multiple sclerosis. Fingolimod (trade name Gilenya, Novartis) is metabolized by sphingosine kinase to the active metabolite, fingolimod-phosphate. Fingolimod-phosphate is a sphingosine 1-phosphate receptor modulator, and binds with high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5. Fingolimod-phosphate blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which fingolimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system. Fingolimod was approved as a first-in-class, orally active drug for relapsing multiple sclerosis in 2010, and its applications in other disease conditions are currently under clinical trials.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Sphingosine 1-phosphate receptor Edg-1 16	Agonist 2,752	0.84 µM [IC50]
Sphingosine 1-phosphate receptor Edg-8 13	Agonist 2,752	2.1 µM [IC50]
Sphingosine 1-phosphate receptor Edg-6 13	Agonist 2,752	0.3 nM [EC50]
Sphingosine 1-phosphate receptor Edg-3 3	Agonist 2,752	0.3 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Multiple sclerosis 107	Primary		Approved 8,583	GILENYA

C_max

Value	Dose	Co-administered	Analyte	Population
0.65 ng/mL	1 mg single, oral		FINGOLIMOD plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
149 ng × h/mL	1 mg single, oral		FINGOLIMOD plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
7 h	1 mg single, oral		FINGOLIMOD plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
14 mg single, oral Overdose	unhealthy, 33 years	Other AEs: Bradycardia, Hypotension...
1.25 mg 1 times / day steady, oral Highest studied dose	unhealthy, 36.0 years (range: 18–55 years)	Other AEs: Appendicitis, Urinary tract infection...
0.5 mg 1 times / day multiple, oral Recommended	unhealthy, 37 years	Disc. AE: Transaminases increased...
3.5 mg single, oral Highest studied dose	unhealthy, 43.2 years	Other AEs: Bradycardia, Carbon monoxide diffusing capacity decreased...
40 mg single, oral Overdose	unhealthy	Other AEs: Chest tightness...

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AEs

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AE	Significance	Dose	Population
Bradycardia	1 patient	14 mg single, oral Overdose	unhealthy, 33 years
Hypotension	1 patient	14 mg single, oral Overdose	unhealthy, 33 years
Hyperlipidemia	10.9%	1.25 mg 1 times / day steady, oral Highest studied dose	unhealthy, 36.0 years (range: 18–55 years)
Leukopenia	10.9%	1.25 mg 1 times / day steady, oral Highest studied dose	unhealthy, 36.0 years (range: 18–55 years)
Diarrhea	13%	1.25 mg 1 times / day steady, oral Highest studied dose	unhealthy, 36.0 years (range: 18–55 years)

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,946 inhibitor 2,252 inducer 1,087	inhibitor 2,438 inducer 440	inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2,153 CYP2A6 879 CYP2C19 2,057 CYP2E1 1,060 CYP4A9/11 35 CYP2B6 926 CYP3A4/5 296 CYP2C8 1,057 BSEP 550 MRP2 499 P-gp 1,741 OATP1B1 1,079 OATP1B3 961 NTCP 39	CYP2E1 729 CYP1A1 389 CYP2J2 71 FMO3 77	CYP1A2 832 CYP2B6 669 CYP2C8 198 CYP2C19 329 P-gp 301

Drug as perpetrator

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Target	Modality	Activity	Metabolite
CYP1A2 2,333	inhibitor 4,027	no [IC50 >10 uM]	AML627 3
CYP1A2 2,333	inhibitor 4,027	no [IC50 >10 uM]	AML629 3
CYP2A6 911	inhibitor 4,027	no [IC50 >10 uM]	AML627 3
CYP2A6 911	inhibitor 4,027	no [IC50 >10 uM]	AML629 3
CYP2C19 2,141	inhibitor 4,027	no [IC50 >10 uM]	AML627 3

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Drug as victim

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Target	Modality	Activity	Clinical evidence
CYP3A4 1,946	substrate 4,014	minor [Km 107 uM]	unlikely (co-administration study)
CYP2E1 729	substrate 4,014	minor [Km 73 uM]
FMO3 77	substrate 4,014	no
CYP1A1 389	substrate 4,014	yes [Km 117 uM]
CYP2J2 71	substrate 4,014	yes [Km 76 uM]

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237
hERG 2,263	inhibitor 2,237		FTY720-P 3

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63115	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63115
ChemicalBook	CB92498299	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB92498299
eMolecules	6843670	https://www.emolecules.com/cgi-bin/more?vid=6843670
MolPort	MolPort-003-847-513	https://www.molport.com/shop/molecule-link/MolPort-003-847-513
ZINC	ZINC000001542002	http://zinc15.docking.org/substances/ZINC000001542002

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PubMed

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Title	Date	PubMed
Immunosuppressive drugs in paediatric liver transplantation.	2001	11220404
FTY720, a novel immunosuppressive agent with insulinotropic activity, prolongs graft survival in a mouse islet transplantation model.	2001 Feb-Mar	11267010
FTY720 prevents chronic rejection of rat heterotopic cardiac allografts.	2001 Feb-Mar	11266948
FTY720 alters lymphocyte homing and protects allografts without inducing general immunosuppression.	2001 Feb-Mar	11266942
New immunosuppressive drugs: an update.	2001 Mar	11224744

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Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose of GILENYA is 0.5 mg orally once-daily. Fingolimod doses higher than 0.5 mg are associated with a greater incidence of adverse reactions without additional benefit. GILENYA can be taken with or without food.

Route of Administration: Oral

In Vitro Use Guide

Astrocytes derived from human fetal CNS specimens and maintained in dissociated cultures were exposed to 100 nM of the biologically active form of Fingolimod (FTY720) over a dosing regimen that ranged from a single exposure (with or without washout after 1 h) to daily exposures up to 5 days, a single addition of FTY720 inhibited subsequent S1PR ligand-induced pERK1/2 signaling for >24 h. Daily FTY720 treatments (3-5 days) maintained this effect together with a loss of proliferative responses to the natural ligand S1P. Repeated FTY720 dosing concurrently maintained a functional cell response as measured by the inhibition of intracellular calcium release when stimulated by the cytokine IL-1β. Recurrent FTY720 treatments did not inhibit serum- or IL-1β-induced pERK1/2.

Show entries

Name

Type

Language

TASCENSO

Preferred Name

English

FINGOLIMOD LAURYL SULFATE

Common Name

English

SULFURIC ACID, MONODODECYL ESTER, COMPD. WITH 2-AMINO-2-(2-(4-OCTYLPHENYL)ETHYL)-1,3-PROPANEDIOL (1:1)

Common Name

English

Fingolimod lauryl sulfate [WHO-DD]

Common Name

English

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Code System

Code

Type

Description

PUBCHEM

157010667

PRIMARY

FDA UNII

J3HZQ9BE2S

PRIMARY

RXCUI

2610292

PRIMARY

DAILYMED

J3HZQ9BE2S

PRIMARY

CAS

1967800-35-6

PRIMARY

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ACTIVE MOIETY


					3QN8BYN5QF

FINGOLIMOD

SUBSTANCE RECORD


					J3HZQ9BE2S

FINGOLIMOD LAURYL SULFATE

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

Drug as perpetrator