Name: GSK1349572 (Dolutegravir)
Brand: Selleck Chemicals
SKU: S2667
Rating: 5 (33 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.76%

99.76

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

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Incubatietijd	Activiteitsbeschrijving	PMID
MDCK2 cells	Function assay		Inhibition of human OCT2 expressed in MDCK2 cells using [14C]metformin as substrate by liquid scintillation counting analysis	23132334
HOS	Antiviral assay	3 hrs	Antiviral activity against HIV-1 harboring wild type integrase infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay, EC50 = 0.0016 μM.	24901667
HEK293T	Antiviral assay	2 days	Antiviral activity against pseudo Human immunodeficiency virus infected in HEK293T cells after 2 days, IC50 = 0.0017 μM.	23845180
MT4	Antiviral assay	4 to 5 days	Antiviral activity against Human immunodeficiency virus 1 3B infected in human MT4 cells after 4 to 5 days by bioluminescence assay, IC50 = 0.002 μM.	23845180
HOS	Antiviral assay	3 hrs	Antiviral activity against raltegravir-resistant HIV-1 harboring integrase N155H mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay, EC50 = 0.0036 μM.	24901667
HOS	Antiviral assay	3 hrs	Antiviral activity against raltegravir-resistant HIV-1 harboring integrase Y143R mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay, EC50 = 0.0043 μM.	24901667
HOS	Antiviral assay	3 hrs	Antiviral activity against raltegravir-resistant HIV-1 harboring integrase G140S/Q148H double mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay, EC50 = 0.0058 μM.	24901667
HOS	Antiviral assay	3 hrs	Antiviral activity against INSTI-resistant HIV-1 harboring integrase R263K mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay, EC50 = 0.011 μM.	24901667
HOS	Antiviral assay	3 hrs	Antiviral activity against INSTI-resistant HIV-1 harboring integrase G118R mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay, EC50 = 0.013 μM.	24901667
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 = 0.02 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 = 0.02 μM.	28525279
HEK293T	Antiviral assay	2 days	Antiviral activity against pseudo Human immunodeficiency virus infected in HEK293T cells after 2 days in presence of human serum albumin, IC50 = 0.022 μM.	23845180
MDCK2	Function assay		Inhibition of human OCT2 expressed in MDCK2 cells using [14C]metformin as substrate by liquid scintillation counting analysis, IC50 = 1.9 μM.	23132334
Vero E6	Antiviral assay	2 days	Antiviral efficacy against SARS-CoV-2 (strain BavPat1) in Vero E6 cells assessed by inhibition of viral RNA replication measured by RT-PCR after 2 days, EC50 = 22.04 μM.	ChEMBL
Vero E6	Antiviral assay	2 days	Antiviral efficacy against SARS-CoV-2 (strain BavPat1) in Vero E6 cells assessed by inhibition of viral RNA replication measured by RT-PCR after 2 days, EC90 = 42.81 μM.	ChEMBL
Klik om meer experimentele gegevens over de cellijn te bekijken

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Moleculair gewicht	419.38	Formule	C₂₀H₁₉F₂N₃O₅	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	1051375-16-6	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	GSK1349572,S/GSK1349572			Smiles	CC1CCOC2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)O

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 83 mg/mL (197.91 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Moleculair gewicht
=	×	×

Verdunningscalculator Moleculair gewicht calculator

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.
Clear solution	5%DMSO 1 Corn oil Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	1.050mg/ml (2.50mM)	Taking the 1 mL working solution as an example, add 50 μL of 21 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
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 Formuleringscalculator (Heldere oplossing)

Stap 1: Voer de onderstaande informatie in (Aanbevolen: Een extra dier voor het geval van 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 het gedeelte Oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

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

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toeμL PEG300, mengen en helder maken, voeg vervolgens toeμL Tween 80, mengen en helder maken, voeg vervolgens toe μL ddH₂O, mengen en helder maken.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toe μL Maïsolie, mengen en helder maken.

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. Fysische methoden zoals vortexen, echografie of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Kenmerken	A next-generation and two-metal-binding HIV integrase strand transfer inhibitor.
Targets/IC₅₀/Ki	HIV integrase (Cell-free assay) 2.7 nM
In vitro	Dolutegravir (GSK1349572) shows a potent inhibitory effect on nine clinical isolates from integrase inhibitor-naive HIV-2-infected patients with EC50 ranging from 0.2 nM to 1.4 nM. In vitro, it inhibits recombinant HIV-1 integrase-catalyzed strand transfer with an IC50 of 2.7 nM. Furthermore, this compound potently inhibits HIV replication in cells such as peripheral blood mononuclear cells (PBMCs), MT-4 cells, and CIP4 cells infected with a self-inactivating PHIV lentiviral vector, with EC50 values of 0.51 nM, 0.71 nM, and 2.2 nM, respectively. In vitro, it also exhibits potent activity against five different nonnucleoside reverse transcription inhibitor-resistant or nucleoside reverse transcription inhibitor-resistant viruses, with EC50 ranging from 1.3 nM to 2.1 nM. Similarly to its activity against wild-type virus, it shows equivalent efficacy against two protease inhibitor-resistant viruses, with EC50 values of 0.36 nM and 0.37 nM, respectively.
Kinase Assay	In vitro strand transfer assay
Kinase Assay	De remmende vermogens van Dolutegravir (GSK1349572) en andere INI's worden gemeten in een strengoverdrachtassay met behulp van recombinant HIV Integrase. Een complex van Integrase en gebiotinyleerde voorverwerkte donor-DNA-streptavidine-gecoate scintillation proximity assay (SPA) kralen wordt gevormd door 2 μM gezuiverd recombinant Integrase te incuberen met 0,66 μM gebiotinyleerd donor-DNA-4 mg/ml streptavidine-gecoate SPA-kralen in 25 mM natrium-morfolinepropaansulfonzuur (MOPS) (pH 7,2), 23 mM NaCl en 10 mM MgCl₂ gedurende 5 minuten op 37 °C. Deze kralen worden gecentrifugeerd en voor-geïncubeerd met verdunde INI's gedurende 60 minuten op 37 °C. Vervolgens wordt een ₃H-gelabeld doel-DNA-substraat toegevoegd om een eindconcentratie van 7 nM substraat te verkrijgen, en wordt het strengoverdrachtreactiemengsel geïncubeerd op 37 °C gedurende 25 tot 45 minuten, wat een lineaire toename in de strengoverdracht van donor-DNA naar radioactief gelabeld doel-DNA mogelijk maakt. Het signaal wordt uitgelezen met een Wallac MicroBeta scintillatieplaatlezer.
In vivo	Dolutegravir (GSK1349572), a first-line antiretroviral drug (ARV) used in combination therapy for HIV-1, inhibits MMP activity and has the potential to affect prenatal and postnatal neurodevelopment.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/20827161/ [2] https://pubmed.ncbi.nlm.nih.gov/21115794/ [3] https://pubmed.ncbi.nlm.nih.gov/34390469/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	PMID
Dose-response infectivity curves	NL4.3IN(WT) / NL4.3IN(S230R) virus		29617824

Informatie klinische proef (Clinical Trial Information)

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

NCT-nummer	Rekrutering	Aandoeningen	Sponsor/Medewerkers	Startdatum	Fasen
NCT06281834	Not yet recruiting	Pediatric HIV Infection\|Latent Tuberculosis	Brigham and Women''s Hospital\|APIN Public Health Initiatives\|University of Cape Town	May 2024	Phase 1
NCT05122026	Recruiting	HIV Seropositivity\|Pregnancy\|Tuberculosis Infection	The Aurum Institute NPC\|Johns Hopkins University\|Weill Medical College of Cornell University\|University of Washington	January 17 2024	Phase 1\|Phase 2
NCT05069688	Recruiting	Pediatric HIV Infection\|Tuberculosis Infection	Brigham and Women''s Hospital\|APIN Public Health Initiatives\|University of Cape Town	July 7 2023	Phase 1
NCT05122767	Recruiting	Tuberculosis\|HIV	The Aurum Institute NPC\|Johns Hopkins University	May 24 2023	Phase 1\|Phase 2

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GSK1349572 (Dolutegravir) HIV Integrase-remmer

Moleculair gewicht: 419.38

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie klinische proef (Clinical Trial Information)

GSK1349572 (Dolutegravir) HIV Integrase-remmer

Moleculair gewicht: 419.38

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkconcentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie klinische proef (Clinical Trial Information)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)