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Details

Stereochemistry ACHIRAL
Molecular Formula C20H21FN6O5
Molecular Weight 444.4163
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RALTEGRAVIR

SMILES

CN1C(=O)C(O)=C(N=C1C(C)(C)NC(=O)C2=NN=C(C)O2)C(=O)NCC3=CC=C(F)C=C3

InChI

InChIKey=CZFFBEXEKNGXKS-UHFFFAOYSA-N
InChI=1S/C20H21FN6O5/c1-10-25-26-17(32-10)16(30)24-20(2,3)19-23-13(14(28)18(31)27(19)4)15(29)22-9-11-5-7-12(21)8-6-11/h5-8,28H,9H2,1-4H3,(H,22,29)(H,24,30)

HIDE SMILES / InChI

Description

Raltegravir (RAL, Isentress, formerly MK-0518) is an antiretroviral drug produced by Merck & Co., used to treat HIV and it is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in patients 4 weeks of age and older. Raltegravir inhibits the catalytic activity of HIV-1 integrase, an HIV-1 encoded enzyme that is required r viral replication. Inhibition of integrase prevents the covalent insertion, or integration, of unintegrated linear HIV-1 DNA into the host cell genome preventing the formation of the HIV-1 provirus. The provirus is required to direct the production of progeny virus, so inhibiting integration prevents propagation of the viral infection. Raltegravir did not significantly inhibit human phosphoryl transferases including DNA polymerases α, β, and γ. Coadministration with others drugs that are strong inducers of UGT1A1, such as rifampin, may result in reduced plasma concentrations of raltegravir. The most common adverse reactions of moderate to severe intensity (≥2%) are insomnia, headache, dizziness, nausea and fatigue. Severe, potentially life-threatening, and fatal skin reactions have been reported. This include cases of Stevens-Johnson syndrome and toxic epidermal necrolysis. Hypersensitivity reactions have also been reported and were characterized by rash, constitutional findings, and sometimes, organ dysfunction, including hepatic failure. The major mechanism of clearance of raltegravir in humans is UGT1A1-mediated glucuronidation.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
10.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ISENTRESS
PubMed

PubMed

TitleDatePubMed
Raltegravir susceptibility and fitness progression of HIV type-1 integrase in patients on long-term antiretroviral therapy.
2008
Integrase and integration: biochemical activities of HIV-1 integrase.
2008 Dec 17
Quantitative prediction of human clearance guiding the development of Raltegravir (MK-0518, isentress) and related HIV integrase inhibitors.
2009 Apr
Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV.
2009 Apr
Pharmacologic aspects of new antiretroviral drugs.
2009 Feb
Is dual therapy with raltegravir and protease inhibitors a feasible option in rescue strategy in HIV-1 infection?
2009 Feb 1
Effects of omeprazole on plasma levels of raltegravir.
2009 Feb 15
Quantification of the HIV-integrase inhibitor raltegravir and detection of its main metabolite in human plasma, dried blood spots and peripheral blood mononuclear cell lysate by means of high-performance liquid chromatography tandem mass spectrometry.
2009 Feb 20
Implications of HIV-1 M group polymorphisms on integrase inhibitor efficacy and resistance: genetic and structural in silico analyses.
2009 Jan 13
Preclinical evaluation of GS-9160, a novel inhibitor of human immunodeficiency virus type 1 integrase.
2009 Mar
Patents

Sample Use Guides

In Vivo Use Guide
400 mg film-coated tablet orally, twice daily. During coadministration with rifampin in adults, 800 mg twice daily
Route of Administration: Oral
In Vitro Use Guide
The antiviral activity of Raltegravir was determined in a cell-based HIV-1 replication assay with HeLa-CD4-LTR-β-gal cells. The highest compound concentration tested was 50 μM.
Name Type Language
RALTEGRAVIR
DASH   EMA EPAR   INN   MART.   MI   VANDF   WHO-DD  
INN  
Official Name English
RALTEGRAVIR [MART.]
Common Name English
RALTEGRAVIR [WHO-DD]
Common Name English
RALTEGRAVIR [VANDF]
Common Name English
RALTEGRAVIR [MI]
Common Name English
RALTEGRAVIR [EMA EPAR]
Common Name English
N-(4-FLUOROBENZYL)-5-HYDROXY-1-METHYL-2-(1-METHYL-1-(((5-METHYL-1,3,4-OXADIAZOL-2-YL)CARBONYL)AMINO)ETHYL)-6-OXO-1,6-DIHYDROPYRIMIDINE-4-CARBOXAMIDE
Systematic Name English
RALTEGRAVIR [INN]
Common Name English
4-PYRIMIDINECARBOXAMIDE, N-((4-FLUOROPHENYL)METHYL)-1,6-DIHYDRO-5-HYDROXY-1-METHYL-2-(1-METHYL-1-(((5-METHYL-1,3,4-OXADIAZOL-2-YL)CARBONYL)AMINO)ETHYL)-6-OXO-
Systematic Name English
N-(2-(4-(4-FLUOROBENZYLCARBAMOYL)-5-HYDROXY-1-METHYL-6-OXO-1,6- DIHYDROPYRIMIDIN-2-YL)PROPAN-2-YL)-5-METHYL-1,3,4-OXADIAZOLE-2-CARBOXAMIDE
Systematic Name English
Classification Tree Code System Code
WHO-ATC J05AX08
Created by admin on Tue Mar 06 10:22:54 UTC 2018 , Edited by admin on Tue Mar 06 10:22:54 UTC 2018
NDF-RT N0000175887
Created by admin on Tue Mar 06 10:22:54 UTC 2018 , Edited by admin on Tue Mar 06 10:22:54 UTC 2018
WHO-ATC J05AR16
Created by admin on Tue Mar 06 10:22:53 UTC 2018 , Edited by admin on Tue Mar 06 10:22:53 UTC 2018
EMA ASSESSMENT REPORTS ISENTRESS (AUHTORIZED: HIV INFECTIONS)
Created by admin on Tue Mar 06 10:22:53 UTC 2018 , Edited by admin on Tue Mar 06 10:22:53 UTC 2018
LIVERTOX 830
Created by admin on Tue Mar 06 10:22:54 UTC 2018 , Edited by admin on Tue Mar 06 10:22:54 UTC 2018
WHO-VATC QJ05AX08
Created by admin on Tue Mar 06 10:22:54 UTC 2018 , Edited by admin on Tue Mar 06 10:22:54 UTC 2018
NDF-RT N0000000127
Created by admin on Tue Mar 06 10:22:54 UTC 2018 , Edited by admin on Tue Mar 06 10:22:54 UTC 2018
Code System Code Type Description
EVMPD
SUB25667
Created by admin on Tue Mar 06 10:22:54 UTC 2018 , Edited by admin on Tue Mar 06 10:22:54 UTC 2018
PRIMARY
INN
8842
Created by admin on Tue Mar 06 10:22:54 UTC 2018 , Edited by admin on Tue Mar 06 10:22:54 UTC 2018
PRIMARY
CAS
518048-05-0
Created by admin on Tue Mar 06 10:22:54 UTC 2018 , Edited by admin on Tue Mar 06 10:22:54 UTC 2018
PRIMARY
PUBCHEM
54671008
Created by admin on Tue Mar 06 10:22:53 UTC 2018 , Edited by admin on Tue Mar 06 10:22:53 UTC 2018
PRIMARY SWITZERF
LactMed
518048-05-0
Created by admin on Tue Mar 06 10:22:53 UTC 2018 , Edited by admin on Tue Mar 06 10:22:53 UTC 2018
PRIMARY
NCI_THESAURUS
C72837
Created by admin on Tue Mar 06 10:22:54 UTC 2018 , Edited by admin on Tue Mar 06 10:22:54 UTC 2018
PRIMARY
MESH
C507898
Created by admin on Tue Mar 06 10:22:54 UTC 2018 , Edited by admin on Tue Mar 06 10:22:54 UTC 2018
PRIMARY
HSDB
518048-05-0
Created by admin on Tue Mar 06 10:22:53 UTC 2018 , Edited by admin on Tue Mar 06 10:22:53 UTC 2018
PRIMARY
MERCK INDEX
M9486
Created by admin on Tue Mar 06 10:22:53 UTC 2018 , Edited by admin on Tue Mar 06 10:22:53 UTC 2018
PRIMARY Merck Index
EPA CompTox
518048-05-0
Created by admin on Tue Mar 06 10:22:53 UTC 2018 , Edited by admin on Tue Mar 06 10:22:53 UTC 2018
PRIMARY
DRUG BANK
DB06817
Created by admin on Tue Mar 06 10:22:53 UTC 2018 , Edited by admin on Tue Mar 06 10:22:53 UTC 2018
PRIMARY
ChEMBL
CHEMBL254316
Created by admin on Tue Mar 06 10:22:53 UTC 2018 , Edited by admin on Tue Mar 06 10:22:53 UTC 2018
PRIMARY
WIKIPEDIA
RALTEGRAVIR
Created by admin on Tue Mar 06 10:22:54 UTC 2018 , Edited by admin on Tue Mar 06 10:22:54 UTC 2018
PRIMARY
RXCUI
719872
Created by admin on Tue Mar 06 10:22:53 UTC 2018 , Edited by admin on Tue Mar 06 10:22:53 UTC 2018
PRIMARY RxNorm