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Details

Stereochemistry ACHIRAL
Molecular Formula C17H18N4O2
Molecular Weight 310.3511
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LERSIVIRINE

SMILES

CCc1c(c(CC)n(CCO)n1)Oc2cc(cc(c2)C#N)C#N

InChI

InChIKey=MCPUZZJBAHRIPO-UHFFFAOYSA-N
InChI=1S/C17H18N4O2/c1-3-15-17(16(4-2)21(20-15)5-6-22)23-14-8-12(10-18)7-13(9-14)11-19/h7-9,22H,3-6H2,1-2H3

HIDE SMILES / InChI

Molecular Formula C17H18N4O2
Molecular Weight 310.3511
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20660667 http://adisinsight.springer.com/drugs/800025493

Lersivirine (UK-453,061) is a novel second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI). It binds reverse transcriptase in a distinct way leading to a unique resistance profile. Lersivirine is a second-line NNRTI, which was investigated in a Phase IIb clinical trial. Lersivirine has shown encouraging virologic efficacy in a Phase IIa monotherapy study in NNRTI-naive patients. In a Phase IIb clinical trial in ART naive patients, clinical efficacy of lersivirine was compared with efavirenz, each administered together with tenofovir disoproxil fumarate/emtricitabine. After 48 weeks, lersivirine exhibited a slightly lower virologic response but similar immunologic efficacy. However, the trial was not powered for formal hypothesis testing of noninferiority of lersivirine. The development of lersivirine was recently stopped because the developing company determined that the compound would not provide an improvement over existing NNRTIs.

Originator

Curator's Comment:: # Pfizer

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
118.0 nM [IC50]
0.05 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
979.1 ng/mL
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LERSIVIRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1245.3 ng/mL
750 mg 1 times / day steady-state, oral
dose: 750 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LERSIVIRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1727 ng/mL
2400 mg single, oral
dose: 2400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LERSIVIRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1010 ng/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LERSIVIRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4719.4 ng × h/mL
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LERSIVIRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
6530.1 ng × h/mL
750 mg 1 times / day steady-state, oral
dose: 750 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LERSIVIRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
17750 ng × h/mL
2400 mg single, oral
dose: 2400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LERSIVIRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
4100 ng × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LERSIVIRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5.83 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LERSIVIRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
57.6%
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LERSIVIRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
2400 mg single, oral
Highest studied dose
Dose: 2400 mg
Route: oral
Route: single
Dose: 2400 mg
Sources: Page: p.2410
healthy, ADULT
n = 48
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: FASTED
Population Size: 48
Sources: Page: p.2410
1000 mg 1 times / day multiple, oral
Studied dose
Dose: 1000 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 1 times / day
Co-administed with::
darunavir(100 mg bid for 96 weeks)
ritonavir
Sources: Page: p.213
unhealthy, ADULT
n = 32
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 32
Sources: Page: p.213
Disc. AE: Abdominal distension...
AEs leading to
discontinuation/dose reduction:
Abdominal distension (3.1%)
Sources: Page: p.213
500 mg 2 times / day steady-state, oral
Studied dose
Dose: 500 mg, 2 times / day
Route: oral
Route: steady-state
Dose: 500 mg, 2 times / day
Sources: Page: p.2120
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.2120
750 mg 1 times / day steady-state, oral
Studied dose
Dose: 750 mg, 1 times / day
Route: oral
Route: steady-state
Dose: 750 mg, 1 times / day
Sources: Page: p.2120
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.2120
AEs

AEs

AESignificanceDosePopulation
Abdominal distension 3.1%
Disc. AE
1000 mg 1 times / day multiple, oral
Studied dose
Dose: 1000 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 1 times / day
Co-administed with::
darunavir(100 mg bid for 96 weeks)
ritonavir
Sources: Page: p.213
unhealthy, ADULT
n = 32
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 32
Sources: Page: p.213
PubMed

PubMed

TitleDatePubMed
Pyrazole NNRTIs 4: selection of UK-453,061 (lersivirine) as a development candidate.
2009 Oct 15
Lersivirine, a nonnucleoside reverse transcriptase inhibitor with activity against drug-resistant human immunodeficiency virus type 1.
2010 Oct
Selective killing of human immunodeficiency virus infected cells by non-nucleoside reverse transcriptase inhibitor-induced activation of HIV protease.
2010 Oct 15
Patents

Sample Use Guides

In a placebo-controlled Phase IIa clinical trial, 48 NNRTI naive HIV-infected patients were randomized to receive 10, 30, 100, 500 or 750 mg lersivirine monotherapy once daily or 10, 30, 100 or 500 mg t.i.d for 7 days. All dosing regimens with total daily doses of at least 500 mg achieved similar viral load reductions from baseline to day 8 of at least 1.6 log10 copies/ml.
Route of Administration: Oral
Lersivirine is able to inhibit HIV-1 virus replication, with an EC50 ranging from 5 nM to 35 nM against an MOI ranging from 0.005 to 0.5.
Substance Class Chemical
Created
by admin
on Sat Jun 26 08:23:11 UTC 2021
Edited
by admin
on Sat Jun 26 08:23:11 UTC 2021
Record UNII
R3ZGC15A9A
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LERSIVIRINE
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
LERSIVIRINE [INN]
Common Name English
UK-453061
Code English
UK-453,061
Code English
LERSIVIRINE [USAN]
Common Name English
LERSIVIRINE [WHO-DD]
Common Name English
5-((3,5-DIETHYL-1-(2-HYDROXYETHYL)-1H-PYRAZOL-4-YL)OXY)BENZENE-1,3-DICARBONITRILE
Systematic Name English
1,3-BENZENEDICARBONITRILE, 5-((3,5-DIETHYL-1-(2-HYDROXYETHYL)-1H-PYRAZOL-4-YL)OXY)-
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C97453
Created by admin on Sat Jun 26 08:23:11 UTC 2021 , Edited by admin on Sat Jun 26 08:23:11 UTC 2021
Code System Code Type Description
CAS
473921-12-9
Created by admin on Sat Jun 26 08:23:11 UTC 2021 , Edited by admin on Sat Jun 26 08:23:11 UTC 2021
PRIMARY
INN
9147
Created by admin on Sat Jun 26 08:23:11 UTC 2021 , Edited by admin on Sat Jun 26 08:23:11 UTC 2021
PRIMARY
DRUG BANK
DB11649
Created by admin on Sat Jun 26 08:23:11 UTC 2021 , Edited by admin on Sat Jun 26 08:23:11 UTC 2021
PRIMARY
NCI_THESAURUS
C83872
Created by admin on Sat Jun 26 08:23:11 UTC 2021 , Edited by admin on Sat Jun 26 08:23:11 UTC 2021
PRIMARY
ChEMBL
CHEMBL571987
Created by admin on Sat Jun 26 08:23:11 UTC 2021 , Edited by admin on Sat Jun 26 08:23:11 UTC 2021
PRIMARY
EPA CompTox
473921-12-9
Created by admin on Sat Jun 26 08:23:11 UTC 2021 , Edited by admin on Sat Jun 26 08:23:11 UTC 2021
PRIMARY
FDA UNII
R3ZGC15A9A
Created by admin on Sat Jun 26 08:23:11 UTC 2021 , Edited by admin on Sat Jun 26 08:23:11 UTC 2021
PRIMARY
PUBCHEM
16739244
Created by admin on Sat Jun 26 08:23:11 UTC 2021 , Edited by admin on Sat Jun 26 08:23:11 UTC 2021
PRIMARY
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TARGET ORGANISM->INHIBITOR
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC SINGLE ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC SINGLE ORAL ADMINISTRATION