Details
Stereochemistry | ACHIRAL |
Molecular Formula | C17H11ClF3N5O3 |
Molecular Weight | 425.749 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1C(=O)NN=C1CN2C=CC(=C(OC3=CC(Cl)=CC(=C3)C#N)C2=O)C(F)(F)F
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)
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.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24379202 | https://www.ncbi.nlm.nih.gov/pubmed/24412110
Curator's Comment: # Merck
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL247 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24379202 |
12.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | PIFELTRO Approved UsePIFELTRO, 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 Date2018 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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%) Sources: Page: 3Nausea (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%) |
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%) Sources: Page: 5Creatinine increased (2%) Aspartate aminotransferase increase (4%) Lipase increased (7%) Creatine kinase increased (5%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 |
PubMed
Title | Date | PubMed |
---|---|---|
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
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 Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24379202
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).
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Classification Tree | Code System | Code | ||
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WHO-ATC |
J05AG06
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WHO-ATC |
J05AR24
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C171848
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Doravirine
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DORAVIRINE
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ACTIVE MOIETY