LERSIVIRINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H18N4O2
Molecular Weight	310.3504
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC1=NN(CCO)C(CC)=C1OC2=CC(=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	310.3504
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24128277
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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Reverse transcriptase 8 Target ID: CHEMBL2366516 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20660667	Inhibitor 8297		118.0 nM [IC50]
Human immunodeficiency virus 1 33 Target ID: CHEMBL378 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20660667	Inhibitor 8297		0.05 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 151 Sources: https://clinicaltrials.gov/ct2/show/NCT00824421	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
979.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19779321	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19779321	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22371898	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20124396	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

Value	Dose	Analyte	Population
4719.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19779321	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19779321	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22371898	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20124396	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.83 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20124396	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
57.6% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20124396	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

Dose	Population	Adverse events
2400 mg single, oral Highest studied dose Dose: 2400 mg Route: oral Route: single Dose: 2400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22371898 Page: p.2410	healthy, ADULT n = 48 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 48 Sources: https://pubmed.ncbi.nlm.nih.gov/22371898 Page: p.2410	Sources: https://pubmed.ncbi.nlm.nih.gov/22371898 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: https://pubmed.ncbi.nlm.nih.gov/25350959 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: https://pubmed.ncbi.nlm.nih.gov/25350959 Page: p.213	Disc. AE: Abdominal distension... AEs leading to discontinuation/dose reduction: Abdominal distension (3.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/25350959 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: https://pubmed.ncbi.nlm.nih.gov/19779321 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: https://pubmed.ncbi.nlm.nih.gov/19779321 Page: p.2120	Sources: https://pubmed.ncbi.nlm.nih.gov/19779321 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: https://pubmed.ncbi.nlm.nih.gov/19779321 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: https://pubmed.ncbi.nlm.nih.gov/19779321 Page: p.2120	Sources: https://pubmed.ncbi.nlm.nih.gov/19779321 Page: p.2120

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/25350959 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: https://pubmed.ncbi.nlm.nih.gov/25350959 Page: p.213

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00DBN8	https://www.1pchem.com/search?query=1P00DBN8
AK Scientific	3776AH	https://aksci.com/item_detail.php?cat=3776AH
ApexBio Technology	A3548	https://www.apexbt.com/catalogsearch/result/?q=A3548
AstaTech	40687	http://astatechinc.com/CPSResult.php?CRNO=40687
BLD Pharm	BD630720	http://www.bldpharm.com/search/Search.html?keyword=BD630720
Chem Scene	CS-1191	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1191
ChemShuttle	150792	https://www.chemshuttle.com/catalogsearch/result/?q=150792
Debye Scientific	DA-42388	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-42388
Excenen	EX-A165	http://www.excenen.com/searchresultlist.php?id=EX-A165
Lab Network	LN01342061	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342061
MedChem Express	HY-14267	https://www.medchemexpress.com/search.html?q=HY-14267&ft=&fa=&fp=
MolPort	MolPort-039-139-701	https://www.molport.com/shop/molecule-link/MolPort-039-139-701
MuseChem	I003643	https://www.musechem.com/product/I003643.html
ShangHai Biochempartner	BCP08443	http://www.biochempartner.com/search_BCP08443
eMolecules	45475575	https://orderbb.emolecules.com/search/#?query=45475575
eNovation Chemicals	D320045	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D320045&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-5124616280	https://mcule.com/MCULE-5124616280/

PubMed

Title	Date	PubMed
Selective killing of human immunodeficiency virus infected cells by non-nucleoside reverse transcriptase inhibitor-induced activation of HIV protease.	2010 Oct 15	20950436

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 Dec 16 17:22:39 GMT 2023` Edited by `admin` on `Sat Dec 16 17:22:39 GMT 2023`
Record UNII	R3ZGC15A9A
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LERSIVIRINE

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