solo para uso en investigación

Raltegravir Integrase inhibidor

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

Cat. No.S2005

Raltegravir es un potente inhibidor de la integrase (IN) para WT y S217Q PFV IN con una IC50 de 90 nM y 40 nM en ensayos sin células, respectivamente. Muestra una selectividad más de 1000 veces mayor para HIV-1 IN sobre varias enzimas relacionadas dependientes de Mg2+, como la polimerasa del VHC, la transcriptasa inversa del VIH, la RNaseH del VIH y las polimerasas α, β, γ humanas.

Raltegravir Integrase inhibidor Chemical Structure

Estructura química

Peso molecular: 444.42

Saltar a

Control de calidad

Lote: Pureza: 99.82%

99.82

Dianas relacionadas	Bacterial Antibiotics Anti-infection Fungal Antiviral COVID-19 Parasite Reverse Transcriptase HIV HCV Protease
Otros Integrase Inhibidores	MK-2048 BMS-707035 Lavendustin B Robinetin

Cultivo celular, tratamiento y concentración de trabajo

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Descripción de la actividad	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
Haga clic para ver más datos experimentales de líneas celulares

Información química, almacenamiento y estabilidad

Peso molecular	444.42	Fórmula	C₂₀H₂₁FN₆O₅	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	518048-05-0	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	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

Solubilidad

In vitro
Lote:

DMSO : 89 mg/mL (200.26 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Water : Insoluble

Ethanol : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
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.

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH₂O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción

Características	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 IN de PFV que contiene la sustitución S217H es 10 veces menos susceptible a Raltegravir con una IC50 de 900 nM. La IN de PFV muestra el 10 % de la actividad WT y es inhibida por este compuesto con una IC50 de 200 nM, lo que indica una disminución de ~dos veces en la susceptibilidad al inhibidor de transferencia de cadena de la IN (INSTI) en comparación con la IN WT. La IN de PFV S217Q es tan sensible a este compuesto como la enzima WT. Se metaboliza por glucuronidación, no hepáticamente. Este compuesto tiene una potente actividad in vitro contra el VIH-1, con una concentración inhibitoria del 95 % de 31?0 nM, en cultivos de células linfoides T humanas. También es activo contra el VIH-2 cuando se prueba en células CEMx174, con una IC95 de 6 nM. Su metabolismo ocurre principalmente a través de la glucuronidación. Los medicamentos que son fuertes inductores de la enzima de glucuronidación, UGT1A1, reducen significativamente sus concentraciones y no deben usarse. Exhibe efectos inhibitorios débiles sobre la actividad del citocromo P450 hepático. No induce la expresión de ARN de CYP3A4 ni la actividad de la testosterona 6-β-hidroxilasa dependiente de CYP3A4. Su permeabilidad celular se reduce en presencia de magnesio y calcio. Este compuesto y los inhibidores de transferencia de cadena de la integrase (IN) del VIH-1 (INSTIs) relacionados bloquean eficazmente la replicación viral. En líneas celulares T CD4+ linfoides humanas infectadas agudamente MT-4 y CEMx174, la replicación de SIVmac251 es eficazmente inhibida por este compuesto, que muestra una EC90 en el rango nanomolar bajo.
Ensayo de quinasa	Ensayo de integración de PFV
Ensayo de quinasa	Para los ensayos cuantitativos de transferencia de hebra, el sustrato de ADN donante se forma mediante el recocido de oligonucleótidos de grado HPLC 5′-GACTCACTATAGGGCACGCGTCAAAATTCCATGACA y 5′-ATTGTCATG GAATTTTGACGCGTGCCCTATAGTGAGTC. Las reacciones (40 μL) contienen 0,75 μM de PFV IN, 0,75 μM de ADN donante, 4 nM (300 ng) de ADN diana pGEM9-Zf(−) superenrollado, 125 mM de NaCl, 5 mM de MgSO₄, 4 μM de ZnCl₂, 10 mM de DTT, 0,8 % (vol/vol) de DMSO y 25 mM de BisTris propano–HCl, pH 7,45. Se añade Raltegravir en las concentraciones indicadas. Las reacciones se inician añadiendo 2 μL de PFV IN diluida en 150 mM de NaCl, 2 mM de DTT y 10 mM de Tris-HCl, pH 7,4, y se detienen después de 1 hora a 37 °C añadiendo 25 mM de EDTA y 0,5 % (p/v) de SDS. Los productos de la reacción, desproteinizados por digestión con 20 μg de proteinasa K durante 30 minutos a 37 °C, seguidos de precipitación con etanol, se separan en geles de agarosa al 1,5 % y se visualizan mediante tinción con bromuro de etidio. Los productos de integración se cuantifican mediante PCR cuantitativa en tiempo real, utilizando Platinum SYBR Green qPCR SuperMix y tres cebadores: 5′-CTACTTACTCTAGCTTCCCGGCAAC, 5′-TTCGCCAGTTAATAGTTTGCGCAAC y 5′-GACTCACTATAGGGCACGCGT. Las reacciones de PCR (20 μL) contenían 0,5 μM de cada cebador y 1 μL de producto de reacción de integración diluido. Tras un paso de desnaturalización de 5 minutos a 95 °C, se realizan 35 ciclos en un instrumento de PCR CFX96, utilizando 10 segundos de desnaturalización a 95 °C, 30 segundos de anillamiento a 56 °C y 1 minuto de extensión a 68 °C. Las curvas estándar se generan utilizando diluciones en serie de la reacción de PFV IN WT en ausencia de este compuesto.
In vivo	Raltegravir induce una mejora viro-inmunológica en primates no humanos con infección progresiva por SIVmac251. Un primate no humano muestra una carga viral indetectable después de la monoterapia con este compuesto.
Referencias	[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/

Aplicaciones

Métodos	Biomarcadores	Imágenes	PMID
Western blot	CHOP / ATF-4 / XBP-1 / Lamin B		24625618

Información del ensayo clínico

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
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

Soporte técnico

Instrucciones de manipulación

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

Si tiene alguna otra consulta, por favor deje un mensaje.

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):