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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H20F2N4O2
Molecular Weight 410.4174
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LEMBOREXANT

SMILES

Cc1c(cnc(C)n1)OC[C@]2(C[C@@]2([H])C(=Nc3ccc(cn3)F)O)c4cccc(c4)F

InChI

InChIKey=MUGXRYIUWFITCP-PGRDOPGGSA-N
InChI=1S/C22H20F2N4O2/c1-13-19(11-25-14(2)27-13)30-12-22(15-4-3-5-16(23)8-15)9-18(22)21(29)28-20-7-6-17(24)10-26-20/h3-8,10-11,18H,9,12H2,1-2H3,(H,26,28,29)/t18-,22+/m0/s1

HIDE SMILES / InChI

Molecular Formula C22H20F2N4O2
Molecular Weight 410.4174
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Lemborexant is a dual orexin receptor antagonist, which inhibits orexin by binding competitively to two subtypes of orexin receptors. During normal periods of sleep, orexin system activity is suppressed, suggesting it is possible to purposefully facilitate the initiation and maintenance of sleep by interfering with orexin neurotransmission with lemborexant. Extensive in vitro and non-clinical testing of lemborexant supported the supposition that lemborexant has a low risk of QT prolongation at therapeutic and supratherapeutic exposures in humans. A Phase III study of lemborexant in insomnia is underway, and in addition, Eisai has announced the initiation of Phase II clinical studies of lemborexant in patients with irregular sleep-wake rhythm disorder.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
437 ng/mL
10 μg/kg bw single, oral
dose: 10 μg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
LEMBOREXANT plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
203 ng/mL
25 mg 1 times / day steady-state, oral
dose: 25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LEMBOREXANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
998 ng × h/mL
10 μg/kg bw single, oral
dose: 10 μg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
LEMBOREXANT plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
17 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LEMBOREXANT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, 55 years (range: 18 - 88 years)
Health Status: unhealthy
Age Group: 55 years (range: 18 - 88 years)
Sex: M+F
Sources:
Disc. AE: Somnolence, Nightmares...
AEs leading to
discontinuation/dose reduction:
Somnolence (2.9%)
Nightmares (1.3%)
Palpitations (0.6%)
Sources:
5 mg 1 times / day steady, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
unhealthy, 55 years (range: 18 - 88 years)
Health Status: unhealthy
Age Group: 55 years (range: 18 - 88 years)
Sex: M+F
Sources:
Disc. AE: Somnolence, Nightmares...
AEs leading to
discontinuation/dose reduction:
Somnolence (1%)
Nightmares (0.3%)
Sources:
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
healthy
Health Status: healthy
Sources:
Other AEs: Sleep paralysis...
Other AEs:
Sleep paralysis (moderate, 1 patient)
Sources:
75 mg 1 times / day multiple, oral
Highest studied dose
healthy
Other AEs: Headache, Sleep paralysis...
AEs

AEs

AESignificanceDosePopulation
Palpitations 0.6%
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, 55 years (range: 18 - 88 years)
Health Status: unhealthy
Age Group: 55 years (range: 18 - 88 years)
Sex: M+F
Sources:
Nightmares 1.3%
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, 55 years (range: 18 - 88 years)
Health Status: unhealthy
Age Group: 55 years (range: 18 - 88 years)
Sex: M+F
Sources:
Somnolence 2.9%
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, 55 years (range: 18 - 88 years)
Health Status: unhealthy
Age Group: 55 years (range: 18 - 88 years)
Sex: M+F
Sources:
Nightmares 0.3%
Disc. AE
5 mg 1 times / day steady, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
unhealthy, 55 years (range: 18 - 88 years)
Health Status: unhealthy
Age Group: 55 years (range: 18 - 88 years)
Sex: M+F
Sources:
Somnolence 1%
Disc. AE
5 mg 1 times / day steady, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
unhealthy, 55 years (range: 18 - 88 years)
Health Status: unhealthy
Age Group: 55 years (range: 18 - 88 years)
Sex: M+F
Sources:
Sleep paralysis moderate, 1 patient
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
healthy
Health Status: healthy
Sources:
Headache 1 patient
75 mg 1 times / day multiple, oral
Highest studied dose
healthy
Insomnia 1 patient
75 mg 1 times / day multiple, oral
Highest studied dose
healthy
Sleep paralysis 1 patient
75 mg 1 times / day multiple, oral
Highest studied dose
healthy
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
weak
yes [IC50 24.6 uM]
yes [IC50 7.8 uM]
yes [Ki 25.2 uM]
yes
yes
yes
yes
yes
yes
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: The effect of fluconazole (a moderate CYP3A inhibitor) on the PK of lemborexant was evaluated in Study 012 The lemborexant Cmax, AUC0-t and AUC0-inf values increased by approximately 1.6-, 3.8­ and 4.2-fold, respectively, as compared with lemborexant alone
Page: 47
minor
yes (co-administration study)
Comment: The effect of fluconazole (a moderate CYP3A inhibitor) on the PK of lemborexant was evaluated in Study 012 The lemborexant Cmax, AUC0-t and AUC0-inf values increased by approximately 1.6-, 3.8­ and 4.2-fold, respectively, as compared with lemborexant alone
Page: 47
no
no
no
no
poor
yes
Tox targets
PubMed

PubMed

TitleDatePubMed
In Vitro and In Silico Characterization of Lemborexant (E2006), a Novel Dual Orexin Receptor Antagonist.
2017 Aug
Patents

Patents

Sample Use Guides

5 mg or 10 mg before the time the participant intends to try to sleep
Route of Administration: Oral
The effect of lemborexant on the slow component of delayed rectifier potassium current (IKs) was examined using KCNQ1/KCNE1-CHO cells and a small, not-concentration-dependent inhibition was noted with a peak inhibitory effect of 24% at 10 (uM, and a smaller effect (13%) at 30 uM.
Substance Class Chemical
Created
by admin
on Sat Jun 26 07:51:18 UTC 2021
Edited
by admin
on Sat Jun 26 07:51:18 UTC 2021
Record UNII
0K5743G68X
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LEMBOREXANT
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
DAYVIGO
Brand Name English
(1R,2S)-2-(((2,4-DIMETHYLPYRIMIDIN-5-YL)OXY)METHYL)-2-(3-FLUOROPHENYL)-N-(5-FLUOROPYRIDIN-2-YL)CYCLOPROPANECARBOXAMIDE
Systematic Name English
(1R,2S)-2-((2,4-DIMETHYLPYRIMIDIN-5-YL)OXYMETHYL)-2-(3-FLUOROPHENYL)-N-(5-FLUOROPYRIDIN-2-YL)CYCLOPROPANE-1-CARBOXAMIDE
Systematic Name English
CYCLOPROPANECARBOXAMIDE, 2-(((2,4-DIMETHYL-5-PYRIMIDINYL)OXY)METHYL)-2-(3-FLUOROPHENYL)-N-(5-FLUORO-2-PYRIDINYL)-, (1R,2S)-
Systematic Name English
E2006
Code English
LEMBOREXANT [INN]
Common Name English
E-2006
Code English
LEMBOREXANT [WHO-DD]
Common Name English
LEMBOREXANT [USAN]
Common Name English
Classification Tree Code System Code
DEA NO. 2245
Created by admin on Sat Jun 26 07:51:18 UTC 2021 , Edited by admin on Sat Jun 26 07:51:18 UTC 2021
Code System Code Type Description
INN
9988
Created by admin on Sat Jun 26 07:51:18 UTC 2021 , Edited by admin on Sat Jun 26 07:51:18 UTC 2021
PRIMARY
RXCUI
2272403
Created by admin on Sat Jun 26 07:51:18 UTC 2021 , Edited by admin on Sat Jun 26 07:51:18 UTC 2021
PRIMARY
ChEMBL
CHEMBL3545367
Created by admin on Sat Jun 26 07:51:18 UTC 2021 , Edited by admin on Sat Jun 26 07:51:18 UTC 2021
PRIMARY
FDA UNII
0K5743G68X
Created by admin on Sat Jun 26 07:51:18 UTC 2021 , Edited by admin on Sat Jun 26 07:51:18 UTC 2021
PRIMARY
CAS
1369764-02-2
Created by admin on Sat Jun 26 07:51:18 UTC 2021 , Edited by admin on Sat Jun 26 07:51:18 UTC 2021
PRIMARY
LACTMED
Lemborexant
Created by admin on Sat Jun 26 07:51:18 UTC 2021 , Edited by admin on Sat Jun 26 07:51:18 UTC 2021
PRIMARY
DRUG CENTRAL
5360
Created by admin on Sat Jun 26 07:51:18 UTC 2021 , Edited by admin on Sat Jun 26 07:51:18 UTC 2021
PRIMARY
DRUG BANK
DB11951
Created by admin on Sat Jun 26 07:51:18 UTC 2021 , Edited by admin on Sat Jun 26 07:51:18 UTC 2021
PRIMARY
WIKIPEDIA
Lemborexant
Created by admin on Sat Jun 26 07:51:18 UTC 2021 , Edited by admin on Sat Jun 26 07:51:18 UTC 2021
PRIMARY
NCI_THESAURUS
C166424
Created by admin on Sat Jun 26 07:51:18 UTC 2021 , Edited by admin on Sat Jun 26 07:51:18 UTC 2021
PRIMARY
PUBCHEM
56944144
Created by admin on Sat Jun 26 07:51:18 UTC 2021 , Edited by admin on Sat Jun 26 07:51:18 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
MAJOR
EXCRETED UNCHANGED
URINE
BINDER->LIGAND
Protein binding of lemborexant is approximately 93.2% to 94.0% between 29 ng/mL and 71 ng/mL.
BINDING
METABOLIC ENZYME -> INDUCER
METABOLIC ENZYME -> INHIBITOR
REVERSIBLE INHIBITION
IC50
TARGET -> INHIBITOR
IC50
METABOLIC ENZYME -> INDUCER
TARGET -> INHIBITOR
IC50
METABOLIC ENZYME -> INHIBITOR
REVERSIBLE INHIBITION
IC50
METABOLIC ENZYME -> INHIBITOR
WEAK
TIME-DEPENDENT INHIBITION
Ki
METABOLIC ENZYME -> SUBSTRATE
MINOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC ORAL ADMINISTRATION

Tmax PHARMACOKINETIC HIGH-FAT AND HIGH-CALORIE MEAL

FED CONDITION

Tmax PHARMACOKINETIC