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Raltegravir Integrase inhibitor

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

Kat.-Nr.S2005

Raltegravir ist ein potenter Integrase (IN)-Inhibitor für WT und S217Q PFV IN mit einer IC50 von 90 nM bzw. 40 nM in zellfreien Assays. Es zeigt eine mehr als 1000-fache Selektivität für HIV-1 IN gegenüber mehreren verwandten Mg2+-abhängigen Enzymen wie HCV-Polymerase, HIV-Reverse-Transkriptase, HIV RNaseH und menschlichen α-, β-, γ-Polymerasen.

Raltegravir Integrase inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 444.42

Springe zu

Qualitätskontrolle

Charge: Reinheit: 99.82%

99.82

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

Zellkultur, Behandlung & Arbeitskonzentration

Zelllinien	Assay-Typ	Konzentration	Inkubationszeit	Aktivitätsbeschreibung	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 Informationen, Lagerung & Stabilität

Molekulargewicht	444.42	Formel	C₂₀H₂₁FN₆O₅	Lagerung (Ab dem Eingangsdatum)	3 Jahre-20°CPulver
CAS-Nr.	518048-05-0	SDF herunterladen		Lagerung von Stammlösungen	1 Jahr-80°Cin Lösungsmittel 1 Monat-20°Cin Lösungsmittel
Synonyme	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

Löslichkeit

In vitro
Charge:

DMSO : 89 mg/mL (200.26 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 89 mg/mL (200.26 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 89 mg/mL (200.26 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 89 mg/mL (200.26 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 88 mg/mL (198.01 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritätsrechner

Masse	Konzentration	Volumen	Molekulargewicht
=	×	×

Verdünnungsrechner Molekulargewichtsrechner

In vivo Charge:
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-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie die untenstehenden Informationen ein (Empfohlen: Ein zusätzliches Tier zur Berücksichtigung von Verlusten während des Experiments)

Dosierung: mg/kg Durchschnittsgewicht der Tiere: g Dosiervolumen pro Tier:μL Anzahl der Tiere:

Schritt 2: Geben Sie die In-vivo-Formulierung ein (Dies ist nur der Rechner, keine Formulierung. Bitte kontaktieren Sie uns zuerst, wenn es im Abschnitt "Löslichkeit" keine In-vivo-Formulierung gibt.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

Methode zur Herstellung der DMSO-Stammlösung: mg Wirkstoff vorgelöst in μL DMSO ( Konzentration der Stammlösung mg/mL, Bitte kontaktieren Sie uns zuerst, wenn die Konzentration die DMSO-Löslichkeit der Wirkstoffcharge überschreitet. )

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügenμL PEG300, mischen und klären, dann hinzufügenμL Tween 80, mischen und klären, dann hinzufügen μL ddH₂O, mischen und klären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügen μL Maisöl, mischen und klären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, das/die Lösungsmittel der Reihe nach hinzuzufügen. Sie müssen sicherstellen, dass die bei der vorherigen Zugabe erhaltene Lösung eine klare Lösung ist, bevor Sie mit der Zugabe des nächsten Lösungsmittels fortfahren. Physikalische Methoden wie Vortex, Ultraschall oder ein heißes Wasserbad können zur Unterstützung des Lösens verwendet werden.

Wirkmechanismus

Merkmale	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, das die S217H-Substitution trägt, ist 10-fach weniger empfindlich gegenüber Raltegravir mit einer IC50 von 900 nM. PFV IN zeigt 10 % der WT-Aktivität und wird durch diese Verbindung mit einer IC50 von 200 nM gehemmt, was eine etwa zweifache Abnahme der Empfindlichkeit gegenüber dem IN strand transfer inhibitor (INSTI) im Vergleich zu WT IN anzeigt. S217Q PFV IN ist gegenüber dieser Verbindung genauso empfindlich wie das WT-Enzym. Es wird durch Glucuronidierung metabolisiert, nicht hepatisch. Diese Verbindung hat eine potente In-vitro-Aktivität gegen HIV-1 mit einer 95%igen Hemmkonzentration von 31?0 nM in humanen T-Lymphoidzellkulturen. Sie ist auch gegen HIV-2 aktiv, wenn sie in CEMx174-Zellen getestet wird, mit einer IC95 von 6 nM. Ihr Metabolismus erfolgt hauptsächlich durch Glucuronidierung. Arzneimittel, die starke Induktoren des Glucuronidierungsenzyms UGT1A1 sind, reduzieren ihre Konzentrationen erheblich und sollten nicht verwendet werden. Es zeigt schwache hemmende Wirkungen auf die hepatische Cytochrom-P450-Aktivität. Es induziert weder die CYP3A4-RNA-Expression noch die CYP3A4-abhängige Testosteron-6-β-Hydroxylase-Aktivität. Seine zelluläre Permeabilität ist in Gegenwart von Magnesium und Kalzium reduziert. Diese Verbindung und verwandte HIV-1 Integrase (IN) strand transfer inhibitors (INSTIs) blockieren effizient die virale Replikation. In akut infizierten humanen lymphatischen CD4+-T-Zelllinien MT-4 und CEMx174 wird die SIVmac251-Replikation durch diese Verbindung effizient gehemmt, die eine EC90 im niedrigen nanomolaren Bereich zeigt.
Kinase-Assay	PFV-Integrationsassay
Kinase-Assay	Für quantitative Strangtransferassays wird Donor-DNA-Substrat durch Annealing von HPLC-qualifizierten Oligonukleotiden 5′-GACTCACTATAGGGCACGCGTCAAAATTCCATGACA und 5′-ATTGTCATG GAATTTTGACGCGTGCCCTATAGTGAGTC gebildet. Reaktionen (40 μL) enthalten 0,75 μM PFV IN, 0,75 μM Donor-DNA, 4 nM (300 ng) supercoiled pGEM9-Zf(−) Ziel-DNA, 125 mM NaCl, 5 mM MgSO₄, 4 μM ZnCl₂, 10 mM DTT, 0,8 % (Vol/Vol) DMSO und 25 mM BisTris propan–HCl, pH 7,45. Raltegravir wird in den angegebenen Konzentrationen hinzugefügt. Die Reaktionen werden durch Zugabe von 2 μL PFV IN, verdünnt in 150 mM NaCl, 2 mM DTT und 10 mM Tris-HCl, pH 7,4, initiiert und nach 1 Stunde bei 37 °C durch Zugabe von 25 mM EDTA und 0,5 % (Gew./Vol.) SDS gestoppt. Reaktionsprodukte, deproteinisiert durch Digestion mit 20 μg Proteinase K für 30 Minuten bei 37 °C, gefolgt von Ethanolfällung, werden in 1,5%igen Agarosegelen getrennt und durch Färbung mit Ethidiumbromid sichtbar gemacht. Integrationsprodukte werden mittels quantitativer Echtzeit-PCR unter Verwendung von Platinum SYBR Green qPCR SuperMix und drei Primern quantifiziert: 5′-CTACTTACTCTAGCTTCCCGGCAAC, 5′-TTCGCCAGTTAATAGTTTGCGCAAC und 5′-GACTCACTATAGGGCACGCGT. PCR-Reaktionen (20 μL) enthielten 0,5 μM jedes Primers und 1 μL verdünntes Integrationsreaktionsprodukt. Nach einem 5-minütigen Denaturierungsschritt bei 95 °C werden 35 Zyklen in einem CFX96 PCR-Instrument durchgeführt, wobei 10 Sekunden Denaturierung bei 95 °C, 30 Sekunden Annealing bei 56 °C und 1 Minute Extension bei 68 °C erfolgen. Standardkurven werden unter Verwendung von Seriendilutionen der WT PFV IN-Reaktion in Abwesenheit dieser Verbindung erstellt.
In vivo	Raltegravir induziert eine viro-immunologische Verbesserung bei nicht-humanen Primaten mit fortschreitender SIVmac251-Infektion. Ein nicht-humaner Primat zeigt eine nicht nachweisbare Viruslast nach dieser Verbindung als Monotherapie.
Literatur	[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/

Anwendungen

Methoden	Biomarker	Bilder	PMID
Western blot	CHOP / ATF-4 / XBP-1 / Lamin B		24625618

Klinische Studieninformationen

(Daten von https://clinicaltrials.gov, aktualisiert am 2024-05-22)

NCT-Nummer	Rekrutierung	Erkrankungen	Sponsor/Kooperationspartner	Startdatum	Phasen
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

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Wenn Sie weitere Fragen haben, hinterlassen Sie bitte eine Nachricht.

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):