U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C17H11ClF3N5O3
Molecular Weight 425.7497
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DORAVIRINE

SMILES

Cn1c(Cn2ccc(c(c2=O)Oc3cc(cc(c3)Cl)C#N)C(F)(F)F)nnc1O

InChI

InChIKey=ZIAOVIPSKUPPQW-UHFFFAOYSA-N
InChI=1S/C17H11ClF3N5O3/c1-25-13(23-24-16(25)28)8-26-3-2-12(17(19,20)21)14(15(26)27)29-11-5-9(7-22)4-10(18)6-11/h2-6H,8H2,1H3,(H,24,28)

HIDE SMILES / InChI

Molecular Formula C17H11ClF3N5O3
Molecular Weight 425.7497
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Doravirine (MK-1439) is a nonnucleoside inhibitor of HIV reverse transcriptase (NNRTI). It displays excellent activities against not only WT viruses but also a broader panel of NNRTI-resistant viruses. Doravirine is a prescription medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV infection in adults who have never taken HIV medicines before. Doravirine is always used in combination with other HIV medicines.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
12.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PIFELTRO

Approved Use

PIFELTRO, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment history. (1)

Launch Date

1.53558725E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.962 μg/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DORAVIRINE unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
16.1 μg × h/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DORAVIRINE unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
15 h
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DORAVIRINE unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
24%
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DORAVIRINE unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources:
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: M+F
Population Size: 383
Sources:
Disc. AE: Rash...
AEs leading to
discontinuation/dose reduction:
Rash (2 patients)
Sources:
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 3
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 3
Other AEs: Abnormal dreams, Nausea...
Other AEs:
Abnormal dreams (all grades, 1%)
Nausea (all grades, 7%)
Headache (all grades, 6%)
Fatigue (all grades, 6%)
Diarrhea (all grades, 5%)
Abdominal pain (all grades, 5%)
Dizziness (all grades, 3%)
Rash (all grades, 2%)
Insomnia (all grades, 1%)
Sources: Page: 3
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 5
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 5
Other AEs: Bilirubin total increased, Creatinine increased...
Other AEs:
Bilirubin total increased (5%)
Creatinine increased (2%)
Aspartate aminotransferase increase (4%)
Lipase increased (7%)
Creatine kinase increased (5%)
Sources: Page: 5
AEs

AEs

AESignificanceDosePopulation
Rash 2 patients
Disc. AE
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources:
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: M+F
Population Size: 383
Sources:
Abnormal dreams all grades, 1%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 3
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 3
Insomnia all grades, 1%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 3
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 3
Rash all grades, 2%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 3
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 3
Dizziness all grades, 3%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 3
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 3
Abdominal pain all grades, 5%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 3
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 3
Diarrhea all grades, 5%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 3
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 3
Fatigue all grades, 6%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 3
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 3
Headache all grades, 6%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 3
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 3
Nausea all grades, 7%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 3
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 3
Creatinine increased 2%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 5
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 5
Aspartate aminotransferase increase 4%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 5
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 5
Bilirubin total increased 5%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 5
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 5
Creatine kinase increased 5%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 5
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 5
Lipase increased 7%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
NRTIs
Sources: Page: 5
unhealthy, adult
n = 383
Health Status: unhealthy
Condition: HIV-1
Age Group: adult
Sex: unknown
Population Size: 383
Sources: Page: 5
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor.
2014
Discovery of MK-1439, an orally bioavailable non-nucleoside reverse transcriptase inhibitor potent against a wide range of resistant mutant HIV viruses.
2014 Feb 1
Patents

Patents

Sample Use Guides

Recommended dosage: One tablet taken orally once daily with or without food in adult patients. (2.1) Dosage adjustment with rifabutin: One tablet taken twice daily (approximately 12 hours apart). (2.2) Tablets: 100 mg doravirine.
Route of Administration: Oral
In the presence of 50% normal human serum (NHS), Doravirine (MK-1439) showed excellent potency in suppressing the replication of WT HIV-1 virus, with a 95% effective concentration (EC95) of 20 nM, as well as K103N, Y181C, and K103N/Y181C mutant viruses with EC95 of 43, 27, and 55 nM, respectively. MK-1439 exhibited similar antiviral activities against 10 different HIV-1 subtype viruses (a total of 93 viruses).
Substance Class Chemical
Created
by admin
on Fri Jun 25 22:49:42 UTC 2021
Edited
by admin
on Fri Jun 25 22:49:42 UTC 2021
Record UNII
913P6LK81M
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DORAVIRINE
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
DORAVIRINE [MI]
Common Name English
DORAVIRINE [USAN]
Common Name English
DORAVIRINE [WHO-DD]
Common Name English
3-CHLORO-5-((1-((4-METHYL-5-OXO-4,5-DIHYDRO-1H-1,2,4-TRIAZOL-3-YL)METHYL)-2-OXO-4-(TRIFLUOROMETHYL)-1,2-DIHYDROPYRIDIN-3-YL)OXY)BENZONITRILE
Systematic Name English
BENZONITRILE, 3-CHLORO-5-((1-((4,5-DIHYDRO-4-METHYL-5-OXO-1H-1,2,4-TRIAZOL-3-YL)METHYL)-1,2-DIHYDRO-2-OXO-4-(TRIFLUOROMETHYL)-3-PYRIDINYL)OXY)-
Systematic Name English
DELSTRIGO COMPONENT DORAVIRINE
Brand Name English
PIFELTRO
Brand Name English
MK-1439A
Brand Name English
DORAVIRINE COMPONENT OF DELSTRIGO
Brand Name English
MK-1439
Brand Name English
DORAVIRINE [INN]
Common Name English
DORAVIRINE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
WHO-ATC J05AG06
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
WHO-ATC J05AR24
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
Code System Code Type Description
FDA UNII
913P6LK81M
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
PRIMARY
EVMPD
SUB177834
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
PRIMARY
EPA CompTox
1338225-97-0
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
PRIMARY
NCI_THESAURUS
C171848
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
PRIMARY
LACTMED
Doravirine
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
PRIMARY
DRUG BANK
DB12301
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
PRIMARY
CAS
1338225-97-0
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
PRIMARY
PUBCHEM
58460047
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
PRIMARY
WIKIPEDIA
DORAVIRINE
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
PRIMARY
ChEMBL
CHEMBL2364608
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
PRIMARY
INN
9797
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
PRIMARY
DRUG CENTRAL
5295
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
PRIMARY
MERCK INDEX
M12084
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
PRIMARY
RXCUI
2055755
Created by admin on Fri Jun 25 22:49:42 UTC 2021 , Edited by admin on Fri Jun 25 22:49:42 UTC 2021
ALTERNATIVE
Related Record Type Details
EXCRETED UNCHANGED
Major route of elimination is metabolism.
METABOLIC ENZYME -> SUBSTRATE
MAJOR
INHIBITOR->TARGET ORGANISM
BINDER->LIGAND
BINDING
TARGET ORGANISM->INHIBITOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC