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

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Kvalitetskontroll (Quality Control)

Batch: Renhet: 99.76%

99.76

Relaterade mål	Bacterial Antibiotics Anti-infection Fungal Antiviral COVID-19 Parasite Reverse Transcriptase HIV HCV Protease
Övrigt Integrase Inhibitorer	MK-2048 BMS-707035 Lavendustin B Robinetin

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Cellinjer	Analystyp	Inkubationstid	Aktivitetsbeskrivning	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
Klicka för att visa mer experimentella data för cellinjer

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Molekylvikt	419.38	Formel	C₂₀H₁₉F₂N₃O₅	Lagring (från mottagningsdatumet)	3 år-20°Cpulver
CAS-nr	1051375-16-6	Ladda ner SDF		Lagring av stamlösningar	1 år-80°Ci lösningsmedel 1 månad-20°Ci lösningsmedel
Synonymer	GSK1349572,S/GSK1349572			Smiles	CC1CCOC2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)O

Löslighet (Solubility)

In vitro
Batch:

DMSO : 83 mg/mL (197.91 mM)
(Fuktkontaminerad DMSO kan minska lösligheten. Använd färk, vattenfri DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritetsräknare

Massa	Koncentration	Volym	Molekylvikt
=	×	×

Utspädningsräknare Molekylviktsräknare

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 Validerad av Selleck-laboratorier. Om du behöver justeringar av denna formulering, kontakta vårt säljteam för skräddarsydd testning.	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-formuleringsräknare (Klar lösning)

Steg 1: Ange information nedan (Rekommenderas: Ett extra djur för att ta hänsyn till förluster under experimentet)

Dosering: mg/kg Djurens medelvikt: g Doseringsvolym per djur:μL Antal djur:

Steg 2: Ange in vivo-formuleringen (Detta är endast räknaren, inte formuleringen. Vänligen kontakta oss först om det inte finns någon in vivo-formulering i löslighetsavsnittet.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Beräkningsresultat:

Arbetskoncentration: mg/ml;

Metod för att bereda DMSO-stamlösning: mg substans förlöst i μL DMSO ( Stamlösningskoncentration mg/mL, Vänligen kontakta oss först om koncentrationen överskrider DMSO-lösligheten för denna batch av substansen. )

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedanμL PEG300, blanda och klarna, tillsätt sedanμL Tween 80, blanda och klarna, tillsätt sedan μL ddH₂O, blanda och klarna.

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedan μL Majsolja, blanda och klarna.

Obs: 1. Se till att vätskan är klar innan du tillsätter nästa lösningsmedel.
2. Se till att tillsätta lösningsmedlet/lösningsmedlen i ordning. Du måste se till att lösningen som erhålls i föregående tillsats är en klar lösning innan du fortsätter att tillsätta nästa lösningsmedel. Fysiska metoder som vortex, ultraljud eller varmt vattenbad kan användas för att underlätta upplösningen.

Verkningsmekanism (Mechanism of Action)

Egenskaper	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.
Kinasanalys	In vitro-analys av strängöverföring
Kinasanalys	Den hämmande styrkan hos Dolutegravir (GSK1349572) och andra INI:er mäts i en strängöverföringsanalys med användning av rekombinant HIV Integrase. Ett komplex av Integrase och biotinylerat förbearbetat donator-DNA-streptavidin-belagda scintillation proximity assay (SPA)-pärlor bildas genom att inkubera 2 μM renat rekombinant Integrase med 0,66 μM biotinylerat donator-DNA-4 mg/mL streptavidin-belagda SPA-pärlor i 25 mM natriummorfolinpropansulfonsyra (MOPS) (pH 7,2), 23 mM NaCl och 10 mM MgCl₂ i 5 minuter vid 37 °C. Dessa pärlor centrifugeras ner och förinkuberas med utspädda INI:er i 60 minuter vid 37 °C. Därefter tillsätts ett ₃H-märkt mål-DNA-substrat för att ge en slutkoncentration på 7 nM substrat, och strängöverföringsreaktionsblandningen inkuberas vid 37 °C i 25 till 45 minuter, vilket möjliggör en linjär ökning av strängöverföringen av donator-DNA till radiomärkt mål-DNA. Signalen läses av med en Wallac MicroBeta scintillationsplattläsare.
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.
Referenser	[1] https://pubmed.ncbi.nlm.nih.gov/20827161/ [2] https://pubmed.ncbi.nlm.nih.gov/21115794/ [3] https://pubmed.ncbi.nlm.nih.gov/34390469/

Applikationer (Applications)

Metoder	Biomarkörer	Bilder	PMID
Dose-response infectivity curves	NL4.3IN(WT) / NL4.3IN(S230R) virus		29617824

Klinisk prövningsinformation (Clinical Trial Information)

(data från https://clinicaltrials.gov, uppdaterad den 2024-05-22)

NCT-nummer	Rekrytering	Tillstånd	Sponsor/Samarbetspartners	Startdatum	Faser
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

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):

GSK1349572 (Dolutegravir) HIV Integrase hämmare

Molekylvikt: 419.38

Kvalitetskontroll (Quality Control)

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Löslighet (Solubility)

Molaritetsräknare

In vivo-formuleringsräknare (Klar lösning)

Verkningsmekanism (Mechanism of Action)

Applikationer (Applications)

Klinisk prövningsinformation (Clinical Trial Information)

GSK1349572 (Dolutegravir) HIV Integrase hämmare

Molekylvikt: 419.38

Kvalitetskontroll (Quality Control)

Cellodling, behandling & arbetskoncentration (Cell Culture, Treatment & Working Concentration)

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Löslighet (Solubility)

Molaritetsräknare

In vivo-formuleringsräknare (Klar lösning)

Verkningsmekanism (Mechanism of Action)

Applikationer (Applications)

Klinisk prövningsinformation (Clinical Trial Information)

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)