TASIMELTEON

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H19NO2
Molecular Weight	245.3169
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CCC(=O)NC[C@@H]1C[C@H]1C2=C3CCOC3=CC=C2

InChI

InChIKey=PTOIAAWZLUQTIO-GXFFZTMASA-N

InChI=1S/C15H19NO2/c1-2-15(17)16-9-10-8-13(10)11-4-3-5-14-12(11)6-7-18-14/h3-5,10,13H,2,6-9H2,1H3,(H,16,17)/t10-,13+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C15H19NO2
Molecular Weight	245.3169
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Tasimelteon, developed by Vanda Pharmaceuticals Inc under license from Bristol-Myers Squibb Co, is a melatonin receptor agonist. Tasimelteon differs structurally from melatonin and drugs with known melatonin agonist activity, in particular by its distinct aromatic group and linker. Tasimelteon bears also no structural relationship to any other approved active substance. Tasimelteon is presumably acts through activation of MT1 and MT2 G-protein coupled receptors, which are involved primarily in inhibition of neuronal firing and phase shift of circadian rhythms. Tasimelteon is approved for the treatment of Non24-Hour Sleep-Wake Disorder.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Melatonin receptor type 1B 4	Agonist 2,678		0.0692 nM [Ki]
Melatonin receptor type 1A 3	Agonist 2,678		0.304 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Sleep disorders, circadian rhythm 3	Primary		Approved 8,429	HETLIOZ

C_max

Value	Dose	Analyte	Population
12 ng/mL	1 mg 1 times / day steady-state, oral	TASIMELTEON plasma	Homo sapiens
394 ng/mL	150 mg single, oral	TASIMELTEON plasma	Homo sapiens
873 ng/mL	150 mg 1 times / day steady-state, oral	TASIMELTEON plasma	Homo sapiens
173 ng/mL	50 mg single, oral	TASIMELTEON plasma	Homo sapiens
33 ng/mL	10 mg single, oral	TASIMELTEON plasma	Homo sapiens
261 ng/mL	50 mg 1 times / day steady-state, oral	TASIMELTEON plasma	Homo sapiens
5 ng/mL	1 mg single, oral	TASIMELTEON plasma	Homo sapiens
51 ng/mL	10 mg 1 times / day steady-state, oral	TASIMELTEON plasma	Homo sapiens
786 ng/mL	100 mg single, oral	TASIMELTEON plasma	Homo sapiens
445 ng/mL	100 mg single, oral	TASIMELTEON plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
17 ng × h/mL	1 mg 1 times / day steady-state, oral	TASIMELTEON plasma	Homo sapiens
1823 ng × h/mL	150 mg single, oral	TASIMELTEON plasma	Homo sapiens
3797 ng × h/mL	150 mg 1 times / day steady-state, oral	TASIMELTEON plasma	Homo sapiens
426 ng × h/mL	50 mg single, oral	TASIMELTEON plasma	Homo sapiens
59 ng × h/mL	10 mg single, oral	TASIMELTEON plasma	Homo sapiens
611 ng × h/mL	50 mg 1 times / day steady-state, oral	TASIMELTEON plasma	Homo sapiens
8 ng × h/mL	1 mg single, oral	TASIMELTEON plasma	Homo sapiens
96 ng × h/mL	10 mg 1 times / day steady-state, oral	TASIMELTEON plasma	Homo sapiens
2269 ng × h/mL	100 mg single, oral	TASIMELTEON plasma	Homo sapiens
2304 ng × h/mL	100 mg single, oral	TASIMELTEON plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
1.49 h	1 mg 1 times / day steady-state, oral	TASIMELTEON plasma	Homo sapiens
2.78 h	150 mg single, oral	TASIMELTEON plasma	Homo sapiens
2.63 h	150 mg 1 times / day steady-state, oral	TASIMELTEON plasma	Homo sapiens
2.37 h	50 mg single, oral	TASIMELTEON plasma	Homo sapiens
1.29 h	10 mg single, oral	TASIMELTEON plasma	Homo sapiens
2.57 h	50 mg 1 times / day steady-state, oral	TASIMELTEON plasma	Homo sapiens
1.75 h	1 mg single, oral	TASIMELTEON plasma	Homo sapiens
1.44 h	10 mg 1 times / day steady-state, oral	TASIMELTEON plasma	Homo sapiens
2.75 h	100 mg single, oral	TASIMELTEON plasma	Homo sapiens
2.06 h	100 mg single, oral	TASIMELTEON plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
20 mg 1 times / day multiple, oral Recommended	unhealthy, 18 - 92 years n = 1346	Disc. AE: Supraventricular extrasystoles, Tachycardia...
20 mg 1 times / day multiple, oral Recommended	unhealthy, 18 - 92 years n = 151	Disc. AE: Supraventricular extrasystoles, Vomiting...
1 mg 1 times / day multiple, oral Studied dose	unhealthy, 18 - 92 years n = 1346	Disc. AE: Local swelling, Disorientation...
10 mg 1 times / day multiple, oral Studied dose	unhealthy, 18 - 92 years n = 1346	Disc. AE: Diarrhoea, Gastritis...
100 mg 1 times / day multiple, oral Studied dose	unhealthy, 18 - 92 years n = 1346	Disc. AE: Vomiting...

Showing 1 to 5 of 11 entries

Previous1 2 3Next

AEs

Show entries

AE	Significance	Dose	Population
ALT increased	0.07% Disc. AE	20 mg 1 times / day multiple, oral Recommended	unhealthy, 18 - 92 years n = 1346
AST increased	0.07% Disc. AE	20 mg 1 times / day multiple, oral Recommended	unhealthy, 18 - 92 years n = 1346
Blood creatine increased	0.07% Disc. AE	20 mg 1 times / day multiple, oral Recommended	unhealthy, 18 - 92 years n = 1346
Cholestasis	0.07% Disc. AE	20 mg 1 times / day multiple, oral Recommended	unhealthy, 18 - 92 years n = 1346
Constipation	0.07% Disc. AE	20 mg 1 times / day multiple, oral Recommended	unhealthy, 18 - 92 years n = 1346

Showing 1 to 5 of 74 entries

Previous1 2 3 4 5…15Next

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737	substrate 1,037 inhibitor 1,767 inducer 389	substrate 1,217 inhibitor 1,852	inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1,524 CYP2B6 810 CYP2C8 911 CYP2C19 1,478 CYP3A4/5 278 OATP1B1 788 OATP1B3 706 OAT1 599 BCRP 699 OCT2 647 OAT3 642 P-gp 1,461	CYP1A2 1,054 CYP1A1 349 CYP2C19 991 OATP1B1 406 OATP1B3 350 P-gp 1,537	CYP3A4/5 124 CYP2C8 168 CYP1A2 701 CYP2B6 547 CYP2C19 293

Drug as perpetrator

Show entries

Target	Modality	Activity	Metabolite
BCRP 773	inhibitor 3,277	no
BCRP 773	inhibitor 3,277	no	M12 1
BCRP 773	inhibitor 3,277	no	M13 2
BCRP 773	inhibitor 3,277	no	M9 2
CYP1A2 1,692	inducer 1,573	no

Showing 1 to 5 of 62 entries

Previous1 2 3 4 5…13Next

Drug as victim

Show entries

Target	Modality	Activity	Clinical evidence
CYP1A2 1,054	substrate 3,367	major	yes (co-administration study)
CYP3A4 1,737	substrate 3,367	major	yes (co-administration study)
CYP1A1 349	substrate 3,367	minor
CYP2C19 991	substrate 3,367	minor
CYP2C9 1,037	substrate 3,367	minor

Showing 1 to 5 of 18 entries

Previous1 2 3 4Next

Tox targets

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

Showing 1 to 1 of 1 entries

Previous1Next

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:79042	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:79042
ChemicalBook	CB41518537	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB41518537
MolPort	MolPort-028-600-027	https://www.molport.com/shop/molecule-link/MolPort-028-600-027
ZINC	ZINC000004392649	http://zinc15.docking.org/substances/ZINC000004392649
eMolecules	28326483	https://www.emolecules.com/cgi-bin/more?vid=28326483

Showing 1 to 5 of 5 entries

Previous1Next

PubMed

Show entries

Title	Date	PubMed
Preclinical pharmacokinetics and metabolism of BMS-214778, a novel melatonin receptor agonist.	2003 Apr	12661062
A systematic, updated review on the antidepressant agomelatine focusing on its melatonergic modulation.	2010 Sep	21358978
Mechanism of action of tasimelteon in non-24 sleep-wake syndrome: treatment for a circadian rhythm disorder in blind patients.	2014 Dec	25422900
Tasimelteon: a selective and unique receptor binding profile.	2015 Apr	25534555
Tasimelteon for the treatment of non-24-hour sleep-wake disorder.	2015 Jan	25685859

Showing 1 to 5 of 5 entries

Previous1Next

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage of HETLIOZ is 20 mg per day taken before bedtime, at the same time every night. Because of individual differences in circadian rhythms, drug effect may not occur for weeks or months. HETLIOZ should be taken without food.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical
Record UNII	SHS4PU80D9
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

TASIMELTEON

Official Name

English

TASIMELTEON [USAN]

Common Name

English

HETLIOZ

Brand Name

English

Tasimelteon [WHO-DD]

Common Name

English

PROPANAMIDE, N-(((1R,2R)-2-(2,3-DIHYDRO-4-BENZOFURANYL)CYCLOPROPYL)METHYL)-

Systematic Name

English

Showing 1 to 5 of 15 entries

Previous1 2 3Next

Show entries

Classification Tree

Code System

Code

Melatonin receptor agonists

WHO-ATC

N05CH03

Established Pharmacologic Class

NDF-RT

N0000175743

Designated/Approved

FDA ORPHAN DRUG

297409

Positive

EU-Orphan Drug

EU/3/10/841

OCCUPATIONAL DISEASES

EMA ASSESSMENT REPORTS

HETLIOZ (AUTHORIZED: SLEEP DISORDERS, CICARDIAN RHYTHM)

Showing 1 to 5 of 7 entries

Previous1 2Next

Show entries

Code System

Code

Type

Description

USAN

SS-70

PRIMARY

DAILYMED

SHS4PU80D9

PRIMARY

FDA UNII

SHS4PU80D9

PRIMARY

PUBCHEM

10220503

PRIMARY

CAS

609799-22-6

PRIMARY

Showing 1 to 5 of 19 entries

Previous1 2 3 4Next

Show entries

Related Record

Type

Details


					L9DP834D1P

CYTOCHROME P450 2C9

METABOLIC ENZYME -> SUBSTRATE

Interaction Type:

MINOR


					SHS4PU80D9

TASIMELTEON

EXCRETED UNCHANGED

Qualification:

FECAL

Amount:

0.04 % (average)


					RES3V2K0VC

MELATONIN MT2 RECEPTOR

TARGET -> AGONIST


					VK4SQL11C0

CYTOCHROME P450 1A2

METABOLIC ENZYME -> SUBSTRATE

Interaction Type:

MAJOR


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Interaction Type:

BINDING

Amount:

90 % (average)

Showing 1 to 5 of 11 entries

Previous1 2 3Next

Show entries

Related Record

Type

Details


					UH8466QZ6U

2-(2-HYDROXY-6-((1R,2R)-2-(PROPIONAMIDOMETHYL)CYCLOPROPYL)PHENYL)ACETIC ACID

METABOLITE INACTIVE -> PARENT

Interaction Type:

MAJOR


					KJ8GMM2HWE

(2S,3S,4S,5R,6S)-3,4,5-TRIHYDROXY-6-((4-((1R,2R)-2-((PROPANOYLAMINO)METHYL)CYCLOPROPYL)-2,3-DIHYDROBENZOFURAN-2-YL)OXY)TETRAHYDROPYRAN-2-CARBOXYLIC ACID

METABOLITE -> PARENT


					YTL2HM2EPM

2-HYDROXY TASIMELTEON, (2S)-

METABOLITE -> PARENT


					UH8466QZ6U

2-(2-HYDROXY-6-((1R,2R)-2-(PROPIONAMIDOMETHYL)CYCLOPROPYL)PHENYL)ACETIC ACID

METABOLITE -> PARENT


					4E33W6K5P4

(2S,3S,4S,5R,6S)-3,4,5-TRIHYDROXY-6-(2-(2-HYDROXYETHYL)-3-((1R,2R)-2-((PROPANOYLAMINO)METHYL)CYCLOPROPYL)PHENOXY)TETRAHYDROPYRAN-2-CARBOXYLIC ACID

METABOLITE -> PARENT

Showing 1 to 5 of 5 entries

Previous1Next

Show entries

Related Record

Type

Details


					SHS4PU80D9

TASIMELTEON

ACTIVE MOIETY

Showing 1 to 1 of 1 entries

Previous1Next

Name	Property Type	Amount	Parameters
Tmax	PHARMACOKINETIC	[0.5 to 3] hours (average)	SINGLE- OR MULTIPLE-DOSE ADMINISTRATION

Volume of Distribution	PHARMACOKINETIC	[0.8 to 1.8] Liters/Kilogram (average)

Biological Half-life	PHARMACOKINETIC	[0.9 to 1.7] hours (average)

SMILES

InChI

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