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Details

Stereochemistry ACHIRAL
Molecular Formula C20H21FN6O5
Molecular Weight 444.4163
Optical Activity NONE
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

Molecular Formula C20H21FN6O5
Molecular Weight 444.4163
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

Primary TargetPharmacologyConditionPotency
10.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ISENTRESS

Cmax

ValueDoseCo-administeredAnalytePopulation
1300 ng/mL
400 mg 2 times / day steady, oral
RALTEGRAVIR plasma
Homo sapiens
830.204 ng/ml
400 mg 2 times / day multiple, oral
RALTEGRAVIR plasma
Homo sapiens
20163 nM
1200 mg single, oral
RALTEGRAVIR plasma
Homo sapiens
142 nM
400 mg 2 times / day multiple, oral
RALTEGRAVIR plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
4070 ng*h/mL
400 mg 2 times / day steady, oral
RALTEGRAVIR plasma
Homo sapiens
14.3 μM × h
400 mg 2 times / day multiple, oral
RALTEGRAVIR plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
7.5 h
1200 mg single, oral
RALTEGRAVIR plasma
Homo sapiens
9 h
400 mg 2 times / day multiple, oral
RALTEGRAVIR plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
17%
400 mg 2 times / day multiple, oral
RALTEGRAVIR plasma
Homo sapiens

Doses

AEs

PubMed

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.
Substance Class Chemical
Record UNII
22VKV8053U
Record Status Validated (UNII)
Record Version