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Raltegravir Integrase inhibiteur

Name: Raltegravir
Brand: Selleck Chemicals
SKU: S2005
Rating: 5 (74 reviews)

N° Cat.S2005

Raltegravir est un puissant inhibiteur de l'intégrase (IN)<> pour WT et S217Q PFV IN avec une IC50 de 90 nM et 40 nM respectivement dans les essais sans cellules. Il présente une sélectivité supérieure à 1000 fois pour l'IN du VIH-1 par rapport à plusieurs enzymes apparentées dépendantes du Mg2+ telles que la polymérase du VHC, la transcriptase inverse du VIH, la RNaseH du VIH et les -, -, -polymérases humaines.

Structure chimique

Poids moléculaire: 444.42

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Contrôle qualité

Lot : Pureté : 99.82%

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NMR

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99.82

Cibles apparentées Bacterial Antibiotics Anti-infection Fungal Antiviral COVID-19 Parasite Reverse Transcriptase HIV HCV Protease

Autre Integrase Inhibiteurs MK-2048 BMS-707035 Lavendustin B Robinetin

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires Type dessai Concentration Temps dincubation Formulation Description de lactivité PMID

MT4 Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in human MT4 cells assessed as inhibition of viral replication, EC50 = 0.0014 μM. 18541726

MT-4 Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in human MT-4 cells assessed as inhibition of viral replication, EC50 = 0.0018 μM. 18160521

MT-4 Antiviral assay Antiviral activity against vesicular stomatitis virus G-pseudotyped Human immunodeficiency virus infected in human MT-4 cells assessed as inhibition of viral replication, EC50 = 0.002 μM. 18160521

MT2 Antiviral assay 3 to 4 days Antiviral activity against HIV1 NL4-3 infected in human MT2 cells measured after 3 to 4 days by luciferase reporter gene assay, EC50 = 0.002 μM. 32081010

MT-2 Antiviral assay Antiviral activity against HIV1 3B infected in human MT-2 cells by two fold dilution method in presence of 10% FBS, EC50 = 0.003 μM. 19104010

MT2 Antiviral assay 5 days Antiviral activity against HIV1 3B infected in human MT2 cells after 5 days by chemiluminescence in presence of fetal bovine serum, EC50 = 0.004 μM. 19285389

HOS Antiviral assay Antiviral activity against HIV1 harboring wild-type integrase infected in human HOS cells, EC50 = 0.004 μM. 21493066

HOS Antiviral assay 3 hrs Antiviral activity against wild-type Human immunodeficiency virus 1 infected in HOS cells preincubated for 3 hrs followed by viral infection measured after 48 hrs by luciferase reporter gene assay, EC50 = 0.004 μM. 24471816

MT2 Antiviral assay 5 days Antiviral activity against HIV1 3B in MT2 cells after 5 days, EC50 = 0.006 μM. 18207398

MT-4 Antiviral assay Antiviral activity against HIV 1 RIN harboring integrase gene infected in MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.006 μM. 18378713

MT4 Antiviral assay Antiviral activity against HIV1 3B infected in human MT4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.006 μM. 24900718

MT4 Antiviral assay Antiviral activity against HIV-1 3B infected in human MT4 cells assessed as protection against virus-induced cytopathic effect by MTT assay, EC50 = 0.006 μM. 24793360

MT4 Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in human MT4 cells assessed as inhibition of virus induced cytopathic effect, EC50 = 0.0061 μM. 20479206

MT4 Function assay 1 hr Inhibition of wild type HIV1 3B infected in human MT4 cells using cells pre-incubated with compound for 1 hr measured 4 days post viral infection by MTT assay, IC50 = 0.0062 μM. 22963135

MT4 Antiviral assay Antiviral activity against HIV1 3B infected in human MT4 cells assessed as reduction of virus-induced cytopathogenicity by MTT assay, EC50 = 0.0064 μM. 19447621

MT-4 Antiviral assay Antiviral activity against HIV 1 NL4.3 harboring integrase L74M mutant infected in human MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.007 μM. 18378713

MT4 Antiviral assay Antiviral activity against HIV1 3B infected in human MT4 cells assessed as inhibition of viral-induced cytopathic effect by MTT assay, EC50 = 0.0078 μM. 28951095

MT-4 Antiviral assay Antiviral activity against HIV1 3B infected in human MT-4 cells by two fold dilution method in presence of 10% FBS, EC50 = 0.008 μM. 19104010

MT-4 Antiviral assay Antiviral activity against HIV 1 NL4.3 integrase S230N mutant infected in human MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.009 μM. 18378713

MT4 Antiviral assay 48 to 72 hrs Antiviral activity against HIV1 infected in human MT4 cells expressing GFP incubated for 48 to 72 hrs in absence of 50% normal human serum by multiple round viral replication kinetics assay, IP = 0.009 μM. 26397965

FL-4 Antiviral assay Antiviral activity against Feline immunodeficiency virus infected in cat FL-4 cells assessed as viral RNA production by RT-qPCR, EC50 = 0.00998 μM. 24813732

MT-4 Antiviral assay Antiviral activity against HIV 1 RIN harboring integrase gene infected in MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay after 20 passages selected in presence of compound, EC50 = 0.01 μM. 18378713

HeLa Antiviral assay 48 hrs Antiviral activity against VSV-G pseudotyped HIV1 lentiviral particles infected in human HeLa cells incubated for 48 hrs by spectrofluorometry, IC50 = 0.01 μM. 22858300

cat FL-4 Antiviral assay 7 days Antiviral activity against Feline immunodeficiency virus infected in cat FL-4 cells assessed as inhibition of viral replication after 7 days by quantitative RT-PCR analysis, EC50 = 0.01 μM. 25702849

cat FL-4 Antiviral assay 7 days Antiviral activity against FIV infected in cat FL-4 cells assessed as reduction in viral RNA level measured after 7 days by qRT-PCR analysis, EC50 = 0.01 μM. 31395510

MT4 Antiviral assay Antiviral activity against HIV2 ROD 3B infected in human MT4 cells assessed as inhibition of viral-induced cytopathic effect by MTT assay, EC50 = 0.011 μM. 28951095

MT4 Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in MT4 cells assessed as protection against virus-induced cytopathic effect measured 5 days post infection by MTT assay, EC50 = 0.0117 μM. 29940462

MT4 Antiviral assay Antiviral activity against HIV1 3B assessed as inhibition of viral-induced cytopathic effect in human MT4 cells, EC50 = 0.013 μM. 18417342

MT4 Antiviral assay Antiviral activity against HIV1 infected in human MT4 cells assessed as inhibition of virus-induced cytopathic effect, EC50 = 0.013 μM. 20630765

MT4 Antiviral assay Antiviral activity against HIV1 3B infected in human MT4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.013 μM. 21227550

BL21(DE3) Function assay 1 hr Inhibition of recombinant HIV-1 integrase stand transfer activity expressed in Escherichia coli BL21(DE3) cells using 32P-labeled DNA substrate after 1 hr by densitometric analysis, IC50 = 0.013 μM. 26451771

MT-4 Antiviral assay Antiviral activity against HIV 1 NL4.3 integrase E92Q mutant infected in human MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.015 μM. 18378713

MT4 Antiviral assay 5 days Antiviral activity against HIV1 3B infected in human MT4 cells incubated for 5 days by MTT assay, EC50 = 0.015 μM. 31324562

MT2 Antiviral assay Antiviral activity against HIV in MT2 cells in presence of 35 mg/mL human serum albumin, EC50 = 0.016 μM. 18207398

MT-4 Antiviral assay 5 days Antiviral activity against HIV1 3B/LAI infected in human MT-4 cells assessed as inhibition of virus-induced cytopathic effect measured survival after 5 days by MTT assay, EC50 = 0.016 μM. 24124919

HeLa-CD4-LTR-beta-gal Antiviral assay 1 day Antiviral activity against HIV-1 3B infected in human HeLa-CD4-LTR-beta-gal cells after 1 day by spectroscopic analysis, EC50 = 0.016 μM. 25629256

MT-2 Antiviral assay Antiviral activity against HIV1 3B infected in human MT-2 cells by two fold dilution method in presence of 10% FBS, HSA and alpha1-AGP, EC50 = 0.018 μM. 19104010

MT4 Antiviral assay Antiviral activity against HIV1 3B in human MT4 cells in presence of 10% heat-activated fetal bovine serum, IC95 = 0.019 μM. 18763751

MT2 Antiviral assay 5 days Antiviral activity against HIV1 3B infected in human MT2 cells after 5 days by chemiluminescence in presence of human serum albumin, EC50 = 0.02 μM. 19285389

MT4 Antiviral assay 5 days Antiviral activity against HIV2 ROD infected in human MT4 cells incubated for 5 days by MTT assay, EC50 = 0.02 μM. 31324562

TZM-b1 Antiviral assay 1 hr Antiviral activity against HIV-1 NL4.3 infected in human TZM-b1 cells pretreated for 1 hr followed by viral infection measured after 2 days by CPRG assay, IC50 = 0.021 μM. 28408224

CEM-SS Antiviral assay 6 days Antiviral activity against HIV1 3B infected in human CEM-SS cells assessed as reduction of virus-induced cytopathic effect after 6 days by MTS assay, EC50 = 0.023 μM. 27283261

HeLa Antiviral assay 3 days Antiviral activity against HIV1 3B infected in human HeLa cells expressing CD4-LTR-beta-gal assessed as inhibition of viral replication after 3 days by reporter gene assay, EC50 = 0.0236 μM. 24684270

HeLa-CD4-LTR-beta-gal Antiviral assay Antiviral activity against HIV-1 3B infected in human HeLa-CD4-LTR-beta-gal cells assessed as inhibition of viral replication by SpectraMax GEMINI-XS plate reader analysis, EC50 = 0.0236 μM. 25961960

HeLa Antiviral assay 2 days Antiviral activity against HIV1 3B infected in human HeLa cells expressing CD4 assessed as inhibition of viral replication after 2 days by beta-galactosidase reporter gene assay, EC50 = 0.024 μM. 24124919

MT-4 Antiviral assay Antiviral activity against HIV 1 RIN HIV 1 RIN harboring integrase gene infected in MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay after 40 passages selected in presence of compound, EC50 = 0.025 μM. 18378713

TZM-bl Antiviral assay 48 hrs Antiviral activity against Human immunodeficiency virus 1 infected in human TZM-bl cells assessed as inhibition of viral replication after 48 hrs by inverted microscopic analysis, EC50 = 0.025 μM. 22154762

MT4 Function assay 1 hr Inhibition of wild type HIV1 3B infected in human MT4 cells using cells pre-incubated with compound for 1 hr measured 4 days post viral infection in presence of 20 mg/ml HSA by MTT assay, IC50 = 0.029 μM. 22963135

P4R5 MAGI Antiviral assay 24 hrs Antiviral activity against HIV1 infected in CD4/CXCR4/CCR5 expressing human P4R5 MAGI cells preincubated with cells for 24 hrs followed by viral infection measured after 48 hrs by beta-galactosidase reporter gene assay, EC50 = 0.03 μM. 30031976

P4R5 Antiviral assay 24 hrs Antiviral activity against HIV1 infected in CD4/CXCR4/CCR5 expressing human P4R5 cells assessed as inhibition of viral replication preincubated with cells for 24 hrs followed by viral infection measured after 48 hrs by beta-galactosidase reporter gene ass, EC50 = 0.03 μM. 28525279

P4R5 Antiviral assay 24 hrs Antiviral activity against HIV1 infected in human P4R5 cells assessed as reduction in viral infection preincubated with cells for 24 hrs followed by viral infection measured after 48 hrs by fluorescence based beta-galactosidase reporter gene based MAGI as, EC50 = 0.03 μM. 29031062

P4R5 Antiviral assay 24 hrs Antiviral activity against HIV-1 infected in human P4R5 cells assessed as reduction in viral replication preincubated for 24 hrs followed by viral infection and measured after 48 hrs by MAGI assay, EC50 = 0.03 μM. 30739822

P4R5 Antiviral assay 24 hrs Antiviral activity against HIV1 infected in human P4R5 cells assessed as reduction of virus replication preincubated with cells for 24 hrs followed by viral infection for 48 hrs by 4-methylumbelliferylgalactoside-based MAGI assay, EC50 = 0.03 μM. 27283261

MT4 Antiviral assay Antiviral activity against HIV1 3B in human MT4 cells in presence of 50% normal human serum, IC95 = 0.031 μM. 18763751

MT4 Antiviral assay 48 to 72 hrs Antiviral activity against HIV1 infected in human MT4 cells expressing GFP incubated for 48 to 72 hrs in presence of 50% normal human serum by multiple round viral replication kinetics assay, IP = 0.053 μM. 26397965

BL21(DE3) Function assay 1 hr Inhibition of LEDGF/p75-dependent full length HIV-1 integrase expressed in Escherichia coli BL21(DE3) cells preincubated for 1 hr further incubated for 90 mins with biotin-labeled donor DNA and target DNA by HTRF assay, IC50 = 0.058 μM. 31442684

MT-4 Antiviral assay Antiviral activity against HIV 1 RIN HIV 1 RIN harboring integrase gene infected in MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay after 60 passages selected in presence of compound, EC50 = 0.068 μM. 18378713

HeLaT4 Antiviral assay Antiviral activity against single-round HIV1 NLX.Lux-R harboring inactivating mutations in env, vpr and carries firefly luciferase gene in place of nef assessed as level of 2 mins magnetic nanopartials-medated infection in human HeLaT4 cells treated for 1, EC91 = 0.073 μM. 21060108

HeLa-T4 Antiviral assay 48 hrs Antiviral activity against single-round HIV1 NLX.Lux-R harboring inactivating mutations in env, vpr and carries firefly luciferase gene in place of nef infected in human HeLa-T4 cells assessed as luciferase activity after 48 hrs by exogenous RT assay, EC50 = 0.077 μM. 21060108

TZM-bl Antiviral assay 48 hrs Antiviral activity against HIV-1 infected in human TZM-bl cells assessed as inhibition of viral replication for 48 hrs by bright-Glo luciferase assay, EC50 = 0.15 μM. 26487913

HOS Antiviral assay 3 hrs Antiviral activity against Human immunodeficiency virus 1 harboring integrase N155H mutant infected in HOS cells preincubated for 3 hrs followed by viral infection measured after 48 hrs by luciferase reporter gene assay, EC50 = 0.154 μM. 24471816

TZM-bl Antiviral assay Antiviral activity against HIV1 NL4.3 infected in human TZM-bl cells measured upto 24 hrs by bright Glo-luciferase reporter gene assay, IC50 = 0.16 μM. 31557609

HOS Antiviral assay 3 hrs Antiviral activity against Human immunodeficiency virus 1 harboring integrase Y143R mutant infected in HOS cells preincubated for 3 hrs followed by viral infection measured after 48 hrs by luciferase reporter gene assay, EC50 = 0.162 μM. 24471816

TZM-bl Antiviral assay 1 hr Antiviral activity against HIV1 NL4.3 infected in human TZM-bl cells expressing CXCR4-tropic incubated for 1 hr prior to infection measured after 48 hrs by luciferase reporter gene assay, IC50 = 0.5 μM. 24291042

TZM-bl Antiviral assay 1 hr Antiviral activity against HIV1 NL4.3 infected in human TZM-bl cells expressing CXCR4-tropic incubated for 1 hr prior to infection measured after 48 hrs by luciferase reporter gene assay, IC50 = 0.50119 μM. 24291042

HeLa-T4 Antiviral assay 48 hrs Antiviral activity against single-round HIV1 NLX.Lux-R harboring inactivating mutations in env, vpr and carries firefly luciferase gene in place of nef infected in human HeLa-T4 cells assessed as luciferase activity after 48 hrs by exogenous RT assay, EC95 = 0.81 μM. 21060108

HOS Antiviral assay 3 hrs Antiviral activity against Human immunodeficiency virus 1 harboring integrase G140S/Q148H double mutant infected in HOS cells preincubated for 3 hrs followed by viral infection measured after 48 hrs by luciferase reporter gene assay, EC50 = 1.9 μM. 24471816

MT2 Antiviral assay 3 to 4 days Antiviral activity against HIV1 NL4-3 harboring G140S/Q148H mutant infected in human MT2 cells measured after 3 to 4 days by luciferase reporter gene assay, EC50 = 2.42 μM. 32081010

HeLaT4 Antiviral assay 24 hrs Antiviral activity against single-round HIV1 NLX.Lux-R harboring inactivating mutations in env, vpr and carries firefly luciferase gene in place of nef assessed as level of infection using human HeLaT4 cells pretreated for 24 hrs followed by exposed to vi, EC50 = 4.6 μM. 21060108

MT4 Cytotoxicity assay 5 days Cytotoxicity in mock-infected human MT4 cells assessed as reduction in cell viability incubated for 5 days by MTT assay, CC50 = 6.51 μM. 31324562

CHO Function assay Inhibition of slow delayed inward rectifying potassium current (Iks) in Chinese Hamster Ovary (CHO) cells expressing hKvLQT1/hminK measured using IonWorks Quattro automated patch clamp platform, IC50 = 25.1189 μM. 25087753

U373-MAGI Antiviral assay 50 or 100 nM 72 hrs Antiviral activity against VSV-G pseudotyped HIV-1 NL4-3 infected in human U373-MAGI cells assessed as reduction in gag level at 50 or 100 nM measured at 72 hrs post infection by qPCR method 27117260

U373-MAGI Antiviral assay 50 or 100 nM 72 hrs Antiviral activity against VSV-G pseudotyped HIV-1 NL4-3 infected in human U373-MAGI cells assessed as reduction in U5-gag level at 50 or 100 nM measured at 72 hrs post infection by qPCR method 27117260

MT2 Antiviral assay 1 uM 30 hrs Antiviral activity against wild-type HIV1 NL4-3 infected infected in human MT2 cells assessed as reduction in HIV1 integrated DNA at 1 uM and measured after 30 hrs post infection by Alu-LTR PCR protocol based method 30996780

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Informations chimiques, stockage et stabilité

Poids moléculaire 444.42 Formule
C₂₀H₂₁FN₆O₅
Stockage (À partir de la date de réception) 3 ans-20°Cpoudre

N° CAS 518048-05-0 Télécharger le SDF Stockage des solutions mères
1 an-80°Cen solvant
1 mois-20°Cen solvant

Synonymes MK-0518 Smiles CC1=NN=C(O1)C(=O)NC(C)(C)C2=NC(=C(C(=O)N2C)O)C(=O)NCC3=CC=C(C=C3)F

Solubilité

In vitro
Lot:

DMSO : 89 mg/mL (200.26 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 89 mg/mL (200.26 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 89 mg/mL (200.26 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 89 mg/mL (200.26 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 88 mg/mL (198.01 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Water : Insoluble

Ethanol : Insoluble

Calculateur de molarité

Masse Concentration Volume Poids moléculaire

= × ×

Calculateur de dilution Calculateur de poids moléculaire

In vivo
Lot:

Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Entrez les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant lexpérience)

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre danimaux :

Étape 2 : Entrez la formulation in vivo (Ceci nest que le calculateur, pas la formulation. Veuillez nous contacter dabord sil ny a pas de formulation in vivo dans la section Solubilité.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter dabord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, ajouter ensuiteμL PEG300, mélanger et clarifier, ajouter ensuiteμL Tween 80, mélanger et clarifier, ajouter ensuite μL ddH₂O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, ajouter ensuite μL Huile de maïs, mélanger et clarifier.

Remarque : 1. Assurez-vous que le liquide est clair avant dajouter le solvant suivant.
2. Assurez-vous dajouter le(s) solvant(s) dans lordre. Vous devez vous assurer que la solution obtenue lors de lajout précédent est une solution claire avant de procéder à lajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie peuvent être utilisées pour faciliter la dissolution.

Mécanisme daction

Fonctionnalités
The 1st approved human immunodeficiency virus type 1 (HIV-1) integrase inhibitor.

Targets/IC₅₀/Ki

Integrase (S217Q PFV)
(Cell-free assay)

40 nM

Integrase (WT PFV)
(Cell-free assay)

90 nM

In vitro
La PFV IN portant la substitution S217H est 10 fois moins sensible à Raltegravir avec une IC50 de 900 nM. La PFV IN affiche 10 % de l'activité WT et est inhibée par ce composé avec une IC50 de 200 nM, indiquant une diminution d'environ deux fois de la sensibilité à l'inhibiteur du transfert de brin de l'IN (INSTI) par rapport à l'IN WT. La PFV IN S217Q est aussi sensible à ce composé que l'enzyme WT. Il est métabolisé par glucuronidation, et non hépatiquement. Ce composé possède une activité in vitro puissante contre le VIH-1, avec une concentration inhibitrice de 95 % de 31?0 nM, dans des cultures de cellules lymphoïdes T humaines. Il est également actif contre le VIH-2 lorsqu'il est testé dans des cellules CEMx174, avec une IC95 de 6 nM. Son métabolisme a lieu principalement par glucuronidation. Les médicaments qui sont de puissants inducteurs de l'enzyme de glucuronidation, UGT1A1, réduisent significativement ses concentrations et ne doivent pas être utilisés. Il présente de faibles effets inhibiteurs sur l'activité du cytochrome P450 hépatique. Il n'induit pas l'expression de l'ARN de CYP3A4 ni l'activité de la testostérone 6- -hydroxylase dépendante du CYP3A4. Sa perméabilité cellulaire est réduite en présence de magnésium et de calcium. Ce composé et les inhibiteurs du transfert de brin de l'intégrase (IN) du VIH-1 (INSTI) apparentés bloquent efficacement la réplication virale. Dans les lignées cellulaires T CD4+ lymphoïdes humaines MT-4 et CEMx174 infectées de manière aiguë, la réplication du SIVmac251 est efficacement inhibée par ce composé, qui présente une EC90 dans la gamme des nanomolaires faibles.

Kinase Assay
Essai d'intégration PFV

Pour les essais quantitatifs de transfert de brin, le substrat d'ADN donneur est formé par l'hybridation d'oligonucléotides de qualité HPLC 5 -GACTCACTATAGGGCACGCGTCAAAATTCCATGACA et 5 -ATTGTCATG GAATTTTGACGCGTGCCCTATAGTGAGTC. Les réactions (40 L) contiennent 0,75 M de PFV IN, 0,75 M d'ADN donneur, 4 nM (300 ng) d'ADN cible pGEM9-Zf( ) surenroulé, 125 mM de NaCl, 5 mM de MgSO , 4 M de ZnCl , 10 mM de DTT, 0,8 % (v/v) de DMSO et 25 mM de BisTris propane HCl, pH 7,45. Raltegravir est ajouté aux concentrations indiquées. Les réactions sont initiées par l'ajout de 2 L de PFV IN dilué dans 150 mM de NaCl, 2 mM de DTT et 10 mM de Tris-HCl, pH 7,4, et arrêtées après 1 heure à 37 °C par l'ajout de 25 mM d'EDTA et 0,5 % (p/v) de SDS. Les produits de réaction, déprotéinés par digestion avec 20 g de protéinase K pendant 30 minutes à 37 °C suivie d'une précipitation à l'éthanol, sont séparés dans des gels d'agarose à 1,5 % et visualisés par coloration au bromure d'éthidium. Les produits d'intégration sont quantifiés par PCR quantitative en temps réel, en utilisant le Platinum SYBR Green qPCR SuperMix et trois amorces : 5 -CTACTTACTCTAGCTTCCCGGCAAC, 5 -TTCGCCAGTTAATAGTTTGCGCAAC et 5 -GACTCACTATAGGGCACGCGT. Les réactions de PCR (20 L) contiennent 0,5 M de chaque amorce et 1 L de produit de réaction d'intégration dilué. Après une étape de dénaturation de 5 minutes à 95 °C, 35 cycles sont effectués dans un instrument PCR CFX96, avec 10 secondes de dénaturation à 95 °C, 30 secondes d'hybridation à 56 °C et 1 minute d'extension à 68 °C. Des courbes standard sont générées en utilisant des dilutions en série de la réaction de la PFV IN WT en l'absence de ce composé.

In vivo
Raltegravir induit une amélioration viro-immunologique chez les primates non humains atteints d'une infection progressive par le SIVmac251. Un primate non humain présente une charge virale indétectable après une monothérapie avec ce composé.

Références

[1] https://pubmed.ncbi.nlm.nih.gov/21030679/

[2] https://pubmed.ncbi.nlm.nih.gov/19231980/

[3] https://pubmed.ncbi.nlm.nih.gov/22450971/

[4] https://pubmed.ncbi.nlm.nih.gov/21719464/

[5] https://pubmed.ncbi.nlm.nih.gov/20233398/

Applications

Méthodes Biomarqueurs Images PMID

Western blot CHOP / ATF-4 / XBP-1 / Lamin B

24625618

Informations sur lessai clinique

(données de https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT Recrutement Conditions Sponsor/Collaborateurs Date de début Phases

NCT04513626 Recruiting
HIV Infections

Centre de Recherches et d''Etude sur la Pathologie Tropicale et le Sida
September 15 2020 Phase 2

NCT03667547 Completed
Human Immunodeficiency Virus (HIV) Infection

Merck Sharp & Dohme LLC
September 27 2018 Phase 4

NCT03174977 Recruiting
HIV-1-infection

University of California San Francisco|Merck Sharp & Dohme LLC
April 1 2018 Early Phase 1

Support technique

Instructions de manipulation

Tel: +1-832-582-8158 Ext:3

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C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Cibles apparentées	Bacterial Antibiotics Anti-infection Fungal Antiviral COVID-19 Parasite Reverse Transcriptase HIV HCV Protease
Autre Integrase Inhibiteurs	MK-2048 BMS-707035 Lavendustin B Robinetin

Lignées cellulaires	Type dessai	Concentration	Temps dincubation	Description de lactivité	PMID
MT4	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 3B infected in human MT4 cells assessed as inhibition of viral replication, EC50 = 0.0014 μM.	18541726
MT-4	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 3B infected in human MT-4 cells assessed as inhibition of viral replication, EC50 = 0.0018 μM.	18160521
MT-4	Antiviral assay			Antiviral activity against vesicular stomatitis virus G-pseudotyped Human immunodeficiency virus infected in human MT-4 cells assessed as inhibition of viral replication, EC50 = 0.002 μM.	18160521
MT2	Antiviral assay		3 to 4 days	Antiviral activity against HIV1 NL4-3 infected in human MT2 cells measured after 3 to 4 days by luciferase reporter gene assay, EC50 = 0.002 μM.	32081010
MT-2	Antiviral assay			Antiviral activity against HIV1 3B infected in human MT-2 cells by two fold dilution method in presence of 10% FBS, EC50 = 0.003 μM.	19104010
MT2	Antiviral assay		5 days	Antiviral activity against HIV1 3B infected in human MT2 cells after 5 days by chemiluminescence in presence of fetal bovine serum, EC50 = 0.004 μM.	19285389
HOS	Antiviral assay			Antiviral activity against HIV1 harboring wild-type integrase infected in human HOS cells, EC50 = 0.004 μM.	21493066
HOS	Antiviral assay		3 hrs	Antiviral activity against wild-type Human immunodeficiency virus 1 infected in HOS cells preincubated for 3 hrs followed by viral infection measured after 48 hrs by luciferase reporter gene assay, EC50 = 0.004 μM.	24471816
MT2	Antiviral assay		5 days	Antiviral activity against HIV1 3B in MT2 cells after 5 days, EC50 = 0.006 μM.	18207398
MT-4	Antiviral assay			Antiviral activity against HIV 1 RIN harboring integrase gene infected in MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.006 μM.	18378713
MT4	Antiviral assay			Antiviral activity against HIV1 3B infected in human MT4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.006 μM.	24900718
MT4	Antiviral assay			Antiviral activity against HIV-1 3B infected in human MT4 cells assessed as protection against virus-induced cytopathic effect by MTT assay, EC50 = 0.006 μM.	24793360
MT4	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 3B infected in human MT4 cells assessed as inhibition of virus induced cytopathic effect, EC50 = 0.0061 μM.	20479206
MT4	Function assay		1 hr	Inhibition of wild type HIV1 3B infected in human MT4 cells using cells pre-incubated with compound for 1 hr measured 4 days post viral infection by MTT assay, IC50 = 0.0062 μM.	22963135
MT4	Antiviral assay			Antiviral activity against HIV1 3B infected in human MT4 cells assessed as reduction of virus-induced cytopathogenicity by MTT assay, EC50 = 0.0064 μM.	19447621
MT-4	Antiviral assay			Antiviral activity against HIV 1 NL4.3 harboring integrase L74M mutant infected in human MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.007 μM.	18378713
MT4	Antiviral assay			Antiviral activity against HIV1 3B infected in human MT4 cells assessed as inhibition of viral-induced cytopathic effect by MTT assay, EC50 = 0.0078 μM.	28951095
MT-4	Antiviral assay			Antiviral activity against HIV1 3B infected in human MT-4 cells by two fold dilution method in presence of 10% FBS, EC50 = 0.008 μM.	19104010
MT-4	Antiviral assay			Antiviral activity against HIV 1 NL4.3 integrase S230N mutant infected in human MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.009 μM.	18378713
MT4	Antiviral assay		48 to 72 hrs	Antiviral activity against HIV1 infected in human MT4 cells expressing GFP incubated for 48 to 72 hrs in absence of 50% normal human serum by multiple round viral replication kinetics assay, IP = 0.009 μM.	26397965
FL-4	Antiviral assay			Antiviral activity against Feline immunodeficiency virus infected in cat FL-4 cells assessed as viral RNA production by RT-qPCR, EC50 = 0.00998 μM.	24813732
MT-4	Antiviral assay			Antiviral activity against HIV 1 RIN harboring integrase gene infected in MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay after 20 passages selected in presence of compound, EC50 = 0.01 μM.	18378713
HeLa	Antiviral assay		48 hrs	Antiviral activity against VSV-G pseudotyped HIV1 lentiviral particles infected in human HeLa cells incubated for 48 hrs by spectrofluorometry, IC50 = 0.01 μM.	22858300
cat FL-4	Antiviral assay		7 days	Antiviral activity against Feline immunodeficiency virus infected in cat FL-4 cells assessed as inhibition of viral replication after 7 days by quantitative RT-PCR analysis, EC50 = 0.01 μM.	25702849
cat FL-4	Antiviral assay		7 days	Antiviral activity against FIV infected in cat FL-4 cells assessed as reduction in viral RNA level measured after 7 days by qRT-PCR analysis, EC50 = 0.01 μM.	31395510
MT4	Antiviral assay			Antiviral activity against HIV2 ROD 3B infected in human MT4 cells assessed as inhibition of viral-induced cytopathic effect by MTT assay, EC50 = 0.011 μM.	28951095
MT4	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 3B infected in MT4 cells assessed as protection against virus-induced cytopathic effect measured 5 days post infection by MTT assay, EC50 = 0.0117 μM.	29940462
MT4	Antiviral assay			Antiviral activity against HIV1 3B assessed as inhibition of viral-induced cytopathic effect in human MT4 cells, EC50 = 0.013 μM.	18417342
MT4	Antiviral assay			Antiviral activity against HIV1 infected in human MT4 cells assessed as inhibition of virus-induced cytopathic effect, EC50 = 0.013 μM.	20630765
MT4	Antiviral assay			Antiviral activity against HIV1 3B infected in human MT4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.013 μM.	21227550
BL21(DE3)	Function assay		1 hr	Inhibition of recombinant HIV-1 integrase stand transfer activity expressed in Escherichia coli BL21(DE3) cells using 32P-labeled DNA substrate after 1 hr by densitometric analysis, IC50 = 0.013 μM.	26451771
MT-4	Antiviral assay			Antiviral activity against HIV 1 NL4.3 integrase E92Q mutant infected in human MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay, EC50 = 0.015 μM.	18378713
MT4	Antiviral assay		5 days	Antiviral activity against HIV1 3B infected in human MT4 cells incubated for 5 days by MTT assay, EC50 = 0.015 μM.	31324562
MT2	Antiviral assay			Antiviral activity against HIV in MT2 cells in presence of 35 mg/mL human serum albumin, EC50 = 0.016 μM.	18207398
MT-4	Antiviral assay		5 days	Antiviral activity against HIV1 3B/LAI infected in human MT-4 cells assessed as inhibition of virus-induced cytopathic effect measured survival after 5 days by MTT assay, EC50 = 0.016 μM.	24124919
HeLa-CD4-LTR-beta-gal	Antiviral assay		1 day	Antiviral activity against HIV-1 3B infected in human HeLa-CD4-LTR-beta-gal cells after 1 day by spectroscopic analysis, EC50 = 0.016 μM.	25629256
MT-2	Antiviral assay			Antiviral activity against HIV1 3B infected in human MT-2 cells by two fold dilution method in presence of 10% FBS, HSA and alpha1-AGP, EC50 = 0.018 μM.	19104010
MT4	Antiviral assay			Antiviral activity against HIV1 3B in human MT4 cells in presence of 10% heat-activated fetal bovine serum, IC95 = 0.019 μM.	18763751
MT2	Antiviral assay		5 days	Antiviral activity against HIV1 3B infected in human MT2 cells after 5 days by chemiluminescence in presence of human serum albumin, EC50 = 0.02 μM.	19285389
MT4	Antiviral assay		5 days	Antiviral activity against HIV2 ROD infected in human MT4 cells incubated for 5 days by MTT assay, EC50 = 0.02 μM.	31324562
TZM-b1	Antiviral assay		1 hr	Antiviral activity against HIV-1 NL4.3 infected in human TZM-b1 cells pretreated for 1 hr followed by viral infection measured after 2 days by CPRG assay, IC50 = 0.021 μM.	28408224
CEM-SS	Antiviral assay		6 days	Antiviral activity against HIV1 3B infected in human CEM-SS cells assessed as reduction of virus-induced cytopathic effect after 6 days by MTS assay, EC50 = 0.023 μM.	27283261
HeLa	Antiviral assay		3 days	Antiviral activity against HIV1 3B infected in human HeLa cells expressing CD4-LTR-beta-gal assessed as inhibition of viral replication after 3 days by reporter gene assay, EC50 = 0.0236 μM.	24684270
HeLa-CD4-LTR-beta-gal	Antiviral assay			Antiviral activity against HIV-1 3B infected in human HeLa-CD4-LTR-beta-gal cells assessed as inhibition of viral replication by SpectraMax GEMINI-XS plate reader analysis, EC50 = 0.0236 μM.	25961960
HeLa	Antiviral assay		2 days	Antiviral activity against HIV1 3B infected in human HeLa cells expressing CD4 assessed as inhibition of viral replication after 2 days by beta-galactosidase reporter gene assay, EC50 = 0.024 μM.	24124919
MT-4	Antiviral assay			Antiviral activity against HIV 1 RIN HIV 1 RIN harboring integrase gene infected in MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay after 40 passages selected in presence of compound, EC50 = 0.025 μM.	18378713
TZM-bl	Antiviral assay		48 hrs	Antiviral activity against Human immunodeficiency virus 1 infected in human TZM-bl cells assessed as inhibition of viral replication after 48 hrs by inverted microscopic analysis, EC50 = 0.025 μM.	22154762
MT4	Function assay		1 hr	Inhibition of wild type HIV1 3B infected in human MT4 cells using cells pre-incubated with compound for 1 hr measured 4 days post viral infection in presence of 20 mg/ml HSA by MTT assay, IC50 = 0.029 μM.	22963135
P4R5 MAGI	Antiviral assay		24 hrs	Antiviral activity against HIV1 infected in CD4/CXCR4/CCR5 expressing human P4R5 MAGI cells preincubated with cells for 24 hrs followed by viral infection measured after 48 hrs by beta-galactosidase reporter gene assay, EC50 = 0.03 μM.	30031976
P4R5	Antiviral assay		24 hrs	Antiviral activity against HIV1 infected in CD4/CXCR4/CCR5 expressing human P4R5 cells assessed as inhibition of viral replication preincubated with cells for 24 hrs followed by viral infection measured after 48 hrs by beta-galactosidase reporter gene ass, EC50 = 0.03 μM.	28525279
P4R5	Antiviral assay		24 hrs	Antiviral activity against HIV1 infected in human P4R5 cells assessed as reduction in viral infection preincubated with cells for 24 hrs followed by viral infection measured after 48 hrs by fluorescence based beta-galactosidase reporter gene based MAGI as, EC50 = 0.03 μM.	29031062
P4R5	Antiviral assay		24 hrs	Antiviral activity against HIV-1 infected in human P4R5 cells assessed as reduction in viral replication preincubated for 24 hrs followed by viral infection and measured after 48 hrs by MAGI assay, EC50 = 0.03 μM.	30739822
P4R5	Antiviral assay		24 hrs	Antiviral activity against HIV1 infected in human P4R5 cells assessed as reduction of virus replication preincubated with cells for 24 hrs followed by viral infection for 48 hrs by 4-methylumbelliferylgalactoside-based MAGI assay, EC50 = 0.03 μM.	27283261
MT4	Antiviral assay			Antiviral activity against HIV1 3B in human MT4 cells in presence of 50% normal human serum, IC95 = 0.031 μM.	18763751
MT4	Antiviral assay		48 to 72 hrs	Antiviral activity against HIV1 infected in human MT4 cells expressing GFP incubated for 48 to 72 hrs in presence of 50% normal human serum by multiple round viral replication kinetics assay, IP = 0.053 μM.	26397965
BL21(DE3)	Function assay		1 hr	Inhibition of LEDGF/p75-dependent full length HIV-1 integrase expressed in Escherichia coli BL21(DE3) cells preincubated for 1 hr further incubated for 90 mins with biotin-labeled donor DNA and target DNA by HTRF assay, IC50 = 0.058 μM.	31442684
MT-4	Antiviral assay			Antiviral activity against HIV 1 RIN HIV 1 RIN harboring integrase gene infected in MT-4 cells assessed as inhibition of virus-induced cytopathic effect by MTT assay after 60 passages selected in presence of compound, EC50 = 0.068 μM.	18378713
HeLaT4	Antiviral assay			Antiviral activity against single-round HIV1 NLX.Lux-R harboring inactivating mutations in env, vpr and carries firefly luciferase gene in place of nef assessed as level of 2 mins magnetic nanopartials-medated infection in human HeLaT4 cells treated for 1, EC91 = 0.073 μM.	21060108
HeLa-T4	Antiviral assay		48 hrs	Antiviral activity against single-round HIV1 NLX.Lux-R harboring inactivating mutations in env, vpr and carries firefly luciferase gene in place of nef infected in human HeLa-T4 cells assessed as luciferase activity after 48 hrs by exogenous RT assay, EC50 = 0.077 μM.	21060108
TZM-bl	Antiviral assay		48 hrs	Antiviral activity against HIV-1 infected in human TZM-bl cells assessed as inhibition of viral replication for 48 hrs by bright-Glo luciferase assay, EC50 = 0.15 μM.	26487913
HOS	Antiviral assay		3 hrs	Antiviral activity against Human immunodeficiency virus 1 harboring integrase N155H mutant infected in HOS cells preincubated for 3 hrs followed by viral infection measured after 48 hrs by luciferase reporter gene assay, EC50 = 0.154 μM.	24471816
TZM-bl	Antiviral assay			Antiviral activity against HIV1 NL4.3 infected in human TZM-bl cells measured upto 24 hrs by bright Glo-luciferase reporter gene assay, IC50 = 0.16 μM.	31557609
HOS	Antiviral assay		3 hrs	Antiviral activity against Human immunodeficiency virus 1 harboring integrase Y143R mutant infected in HOS cells preincubated for 3 hrs followed by viral infection measured after 48 hrs by luciferase reporter gene assay, EC50 = 0.162 μM.	24471816
TZM-bl	Antiviral assay		1 hr	Antiviral activity against HIV1 NL4.3 infected in human TZM-bl cells expressing CXCR4-tropic incubated for 1 hr prior to infection measured after 48 hrs by luciferase reporter gene assay, IC50 = 0.5 μM.	24291042
TZM-bl	Antiviral assay		1 hr	Antiviral activity against HIV1 NL4.3 infected in human TZM-bl cells expressing CXCR4-tropic incubated for 1 hr prior to infection measured after 48 hrs by luciferase reporter gene assay, IC50 = 0.50119 μM.	24291042
HeLa-T4	Antiviral assay		48 hrs	Antiviral activity against single-round HIV1 NLX.Lux-R harboring inactivating mutations in env, vpr and carries firefly luciferase gene in place of nef infected in human HeLa-T4 cells assessed as luciferase activity after 48 hrs by exogenous RT assay, EC95 = 0.81 μM.	21060108
HOS	Antiviral assay		3 hrs	Antiviral activity against Human immunodeficiency virus 1 harboring integrase G140S/Q148H double mutant infected in HOS cells preincubated for 3 hrs followed by viral infection measured after 48 hrs by luciferase reporter gene assay, EC50 = 1.9 μM.	24471816
MT2	Antiviral assay		3 to 4 days	Antiviral activity against HIV1 NL4-3 harboring G140S/Q148H mutant infected in human MT2 cells measured after 3 to 4 days by luciferase reporter gene assay, EC50 = 2.42 μM.	32081010
HeLaT4	Antiviral assay		24 hrs	Antiviral activity against single-round HIV1 NLX.Lux-R harboring inactivating mutations in env, vpr and carries firefly luciferase gene in place of nef assessed as level of infection using human HeLaT4 cells pretreated for 24 hrs followed by exposed to vi, EC50 = 4.6 μM.	21060108
MT4	Cytotoxicity assay		5 days	Cytotoxicity in mock-infected human MT4 cells assessed as reduction in cell viability incubated for 5 days by MTT assay, CC50 = 6.51 μM.	31324562
CHO	Function assay			Inhibition of slow delayed inward rectifying potassium current (Iks) in Chinese Hamster Ovary (CHO) cells expressing hKvLQT1/hminK measured using IonWorks Quattro automated patch clamp platform, IC50 = 25.1189 μM.	25087753
U373-MAGI	Antiviral assay	50 or 100 nM	72 hrs	Antiviral activity against VSV-G pseudotyped HIV-1 NL4-3 infected in human U373-MAGI cells assessed as reduction in gag level at 50 or 100 nM measured at 72 hrs post infection by qPCR method	27117260
U373-MAGI	Antiviral assay	50 or 100 nM	72 hrs	Antiviral activity against VSV-G pseudotyped HIV-1 NL4-3 infected in human U373-MAGI cells assessed as reduction in U5-gag level at 50 or 100 nM measured at 72 hrs post infection by qPCR method	27117260
MT2	Antiviral assay	1 uM	30 hrs	Antiviral activity against wild-type HIV1 NL4-3 infected infected in human MT2 cells assessed as reduction in HIV1 integrated DNA at 1 uM and measured after 30 hrs post infection by Alu-LTR PCR protocol based method	30996780
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Poids moléculaire	444.42	Formule	C₂₀H₂₁FN₆O₅	Stockage (À partir de la date de réception)	3 ans-20°Cpoudre
N° CAS	518048-05-0	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	MK-0518			Smiles	CC1=NN=C(O1)C(=O)NC(C)(C)C2=NC(=C(C(=O)N2C)O)C(=O)NCC3=CC=C(C=C3)F

In vivo Lot:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Fonctionnalités	The 1st approved human immunodeficiency virus type 1 (HIV-1) integrase inhibitor.
Targets/IC₅₀/Ki	Integrase (S217Q PFV) (Cell-free assay) 40 nM Integrase (WT PFV) (Cell-free assay) 90 nM
In vitro	La PFV IN portant la substitution S217H est 10 fois moins sensible à Raltegravir avec une IC50 de 900 nM. La PFV IN affiche 10 % de l'activité WT et est inhibée par ce composé avec une IC50 de 200 nM, indiquant une diminution d'environ deux fois de la sensibilité à l'inhibiteur du transfert de brin de l'IN (INSTI) par rapport à l'IN WT. La PFV IN S217Q est aussi sensible à ce composé que l'enzyme WT. Il est métabolisé par glucuronidation, et non hépatiquement. Ce composé possède une activité in vitro puissante contre le VIH-1, avec une concentration inhibitrice de 95 % de 31?0 nM, dans des cultures de cellules lymphoïdes T humaines. Il est également actif contre le VIH-2 lorsqu'il est testé dans des cellules CEMx174, avec une IC95 de 6 nM. Son métabolisme a lieu principalement par glucuronidation. Les médicaments qui sont de puissants inducteurs de l'enzyme de glucuronidation, UGT1A1, réduisent significativement ses concentrations et ne doivent pas être utilisés. Il présente de faibles effets inhibiteurs sur l'activité du cytochrome P450 hépatique. Il n'induit pas l'expression de l'ARN de CYP3A4 ni l'activité de la testostérone 6- -hydroxylase dépendante du CYP3A4. Sa perméabilité cellulaire est réduite en présence de magnésium et de calcium. Ce composé et les inhibiteurs du transfert de brin de l'intégrase (IN) du VIH-1 (INSTI) apparentés bloquent efficacement la réplication virale. Dans les lignées cellulaires T CD4+ lymphoïdes humaines MT-4 et CEMx174 infectées de manière aiguë, la réplication du SIVmac251 est efficacement inhibée par ce composé, qui présente une EC90 dans la gamme des nanomolaires faibles.
Kinase Assay	Essai d'intégration PFV
Kinase Assay	Pour les essais quantitatifs de transfert de brin, le substrat d'ADN donneur est formé par l'hybridation d'oligonucléotides de qualité HPLC 5 -GACTCACTATAGGGCACGCGTCAAAATTCCATGACA et 5 -ATTGTCATG GAATTTTGACGCGTGCCCTATAGTGAGTC. Les réactions (40 L) contiennent 0,75 M de PFV IN, 0,75 M d'ADN donneur, 4 nM (300 ng) d'ADN cible pGEM9-Zf( ) surenroulé, 125 mM de NaCl, 5 mM de MgSO , 4 M de ZnCl , 10 mM de DTT, 0,8 % (v/v) de DMSO et 25 mM de BisTris propane HCl, pH 7,45. Raltegravir est ajouté aux concentrations indiquées. Les réactions sont initiées par l'ajout de 2 L de PFV IN dilué dans 150 mM de NaCl, 2 mM de DTT et 10 mM de Tris-HCl, pH 7,4, et arrêtées après 1 heure à 37 °C par l'ajout de 25 mM d'EDTA et 0,5 % (p/v) de SDS. Les produits de réaction, déprotéinés par digestion avec 20 g de protéinase K pendant 30 minutes à 37 °C suivie d'une précipitation à l'éthanol, sont séparés dans des gels d'agarose à 1,5 % et visualisés par coloration au bromure d'éthidium. Les produits d'intégration sont quantifiés par PCR quantitative en temps réel, en utilisant le Platinum SYBR Green qPCR SuperMix et trois amorces : 5 -CTACTTACTCTAGCTTCCCGGCAAC, 5 -TTCGCCAGTTAATAGTTTGCGCAAC et 5 -GACTCACTATAGGGCACGCGT. Les réactions de PCR (20 L) contiennent 0,5 M de chaque amorce et 1 L de produit de réaction d'intégration dilué. Après une étape de dénaturation de 5 minutes à 95 °C, 35 cycles sont effectués dans un instrument PCR CFX96, avec 10 secondes de dénaturation à 95 °C, 30 secondes d'hybridation à 56 °C et 1 minute d'extension à 68 °C. Des courbes standard sont générées en utilisant des dilutions en série de la réaction de la PFV IN WT en l'absence de ce composé.
In vivo	Raltegravir induit une amélioration viro-immunologique chez les primates non humains atteints d'une infection progressive par le SIVmac251. Un primate non humain présente une charge virale indétectable après une monothérapie avec ce composé.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/21030679/ [2] https://pubmed.ncbi.nlm.nih.gov/19231980/ [3] https://pubmed.ncbi.nlm.nih.gov/22450971/ [4] https://pubmed.ncbi.nlm.nih.gov/21719464/ [5] https://pubmed.ncbi.nlm.nih.gov/20233398/

Numéro NCT	Recrutement	Conditions	Sponsor/Collaborateurs	Date de début	Phases
NCT04513626	Recruiting	HIV Infections	Centre de Recherches et d''Etude sur la Pathologie Tropicale et le Sida	September 15 2020	Phase 2
NCT03667547	Completed	Human Immunodeficiency Virus (HIV) Infection	Merck Sharp & Dohme LLC	September 27 2018	Phase 4
NCT03174977	Recruiting	HIV-1-infection	University of California San Francisco\|Merck Sharp & Dohme LLC	April 1 2018	Early Phase 1