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Raltegravir Integrase remmer

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

Cat.nr.S2005

Raltegravir is een krachtige integrase (IN)-remmer voor WT en S217Q PFV IN met een IC50 van respectievelijk 90 nM en 40 nM in celvrije assays. Het vertoont een meer dan 1000-voudige selectiviteit voor HIV-1 IN ten opzichte van verschillende gerelateerde Mg2+-afhankelijke enzymen zoals HCV-polymerase, HIV-reverse transcriptase, HIV RNaseH en humane α-, β-, γ-polymerasen.

Raltegravir Integrase remmer Chemical Structure

Chemische structuur

Molecuulgewicht: 444.42

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Kwaliteitscontrole

Batch: Zuiverheid: 99.82%

99.82

Gerelateerde doelwitten	Bacterial Antibiotics Anti-infection Fungal Antiviral COVID-19 Parasite Reverse Transcriptase HIV HCV Protease
Overig Integrase Inhibitoren	MK-2048 BMS-707035 Lavendustin B Robinetin

Celkweek, behandeling & werkzame concentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	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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Chemische informatie, opslag en stabiliteit

Molecuulgewicht	444.42	Formule	C₂₀H₂₁FN₆O₅	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	518048-05-0	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	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

Oplosbaarheid

In vitro
Batch:

DMSO : 89 mg/mL (200.26 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
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Verdunningscalculator Molecuulgewichtcalculator

In vivo Batch:
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.

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Kenmerken	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	PFV IN met de S217H-substitutie is 10 keer minder gevoelig voor Raltegravir met een IC50 van 900 nM. PFV IN vertoont 10% van de WT-activiteit en wordt geremd door deze verbinding met een IC50 van 200 nM, wat duidt op een ~tweevoudige afname in gevoeligheid voor de IN strengoverdrachtsremmer (INSTI) in vergelijking met WT IN. S217Q PFV IN is even gevoelig voor deze verbinding als het WT-enzym. Het wordt gemetaboliseerd door glucuronidatie, niet hepatisch. Deze verbinding heeft een krachtige in vitro activiteit tegen HIV-1, met een 95% remmende concentratie van 31?0 nM, in menselijke T-lymfïde celculturen. Het is ook actief tegen HIV-2 wanneer getest in CEMx174-cellen, met een IC95 van 6 nM. Het metabolisme vindt voornamelijk plaats via glucuronidatie. Geneesmiddelen die sterke inductoren zijn van het glucuronidatie-enzym, UGT1A1, verminderen de concentraties ervan aanzienlijk en mogen niet worden gebruikt. Het vertoont zwakke remmende effecten op de hepatische cytochroom P450-activiteit. Het induceert geen CYP3A4 RNA-expressie of CYP3A4-afhankelijke testosteron 6-β-hydroxylase-activiteit. De cellulaire permeabiliteit wordt verminderd in aanwezigheid van magnesium en calcium. Deze verbinding en gerelateerde HIV-1 integrase (IN) strengoverdrachtsremmers (INSTI's) blokkeren de virale replicatie efficiënt. In acuut geïnfecteerde menselijke lymfoïde CD4+ T-cellijnen MT-4 en CEMx174 wordt de SIVmac251-replicatie efficiënt geremd door deze verbinding, die een EC90 vertoont in het lage nanomolaire bereik.
Kinase Assay	PFV integratie-assay
Kinase Assay	Voor kwantitatieve strengoverdrachtsassays wordt donor-DNA-substraat gevormd door HPLC-kwaliteit oligonucleotiden 5′-GACTCACTATAGGGCACGCGTCAAAATTCCATGACA en 5′-ATTGTCATG GAATTTTGACGCGTGCCCTATAGTGAGTC te annealen. Reacties (40 μL) bevatten 0,75 μM PFV IN, 0,75 μM donor-DNA, 4 nM (300 ng) supercoiled pGEM9-Zf(−) target DNA, 125 mM NaCl, 5 mM MgSO₄, 4 μM ZnCl₂, 10 mM DTT, 0,8% (vol/vol) DMSO en 25 mM BisTris propaan-HCl, pH 7,45. Raltegravir wordt toegevoegd in de aangegeven concentraties. Reacties worden geïnitieerd door toevoeging van 2 μL PFV IN verdund in 150 mM NaCl, 2 mM DTT en 10 mM Tris-HCl, pH 7,4, en gestopt na 1 uur bij 37 °C door toevoeging van 25 mM EDTA en 0,5% (gew/vol) SDS. Reactieproducten, gedeproteïniseerd door digestie met 20 μg proteinase K gedurende 30 minuten bij 37 °C gevolgd door ethanolprecipitatie, worden gescheiden in 1,5% agarosegels en gevisualiseerd door kleuring met ethidiumbromide. Integratieproducten worden gekwantificeerd door kwantitatieve real-time PCR, met behulp van Platinum SYBR Green qPCR SuperMix en drie primers: 5′-CTACTTACTCTAGCTTCCCGGCAAC, 5′-TTCGCCAGTTAATAGTTTGCGCAAC en 5′-GACTCACTATAGGGCACGCGT. PCR-reacties (20 μL) bevatten 0,5 μM van elke primer en 1 μL verdund integratiereactieproduct. Na een denaturatiestap van 5 minuten bij 95 °C worden 35 cycli uitgevoerd in een CFX96 PCR-instrument, met 10 seconden denaturatie bij 95 °C, 30 seconden annealing bij 56 °C en 1 minuut extensie bij 68 °C. Standaardcurves worden gegenereerd met behulp van seriële verdunningen van de WT PFV IN-reactie in afwezigheid van deze verbinding.
In vivo	Raltegravir induceert viro-immunologische verbetering bij niet-menselijke primaten met een voortschrijdende SIVmac251-infectie. Eén niet-menselijke primaat vertoont een ondetecteerbare virale lading na monotherapie met deze verbinding.
Referenties	[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/

Toepassingen

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	CHOP / ATF-4 / XBP-1 / Lamin B		24625618

Informatie over klinische proeven

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
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

Technische ondersteuning

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