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Cabotegravir(GSK744 GSK1265744)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Cabotegravir(GSK744 GSK1265744)图片
CAS NO:1051375-10-0
规格:≥98%
包装与价格:
包装价格(元)
1mg电议
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产品介绍
Cabotegravir (formerly GSK744; GSK1265744; GSK-744; GSK-1265744; Rekambys; Cabenuva) is a potent, orally bioavailable and long-acting inhibitor of HIV integrase approved in 2020 for the treatment and prevention of HIV infection. The combination of cabotegravir and rilpivirine (Cabenuva) was also approved in 2021 for HIV treatment. cabotegravir has a broad spectrum of activity against different HIV subtypes. Cabotegravir inhibits the HIV-1 integrase catalyzed strand transfer reaction with IC50 of 3.0 nM. In resistance passage experiments, integrase enzyme assays, and cellular assays with site-directed molecular (SDM) HIV clones resistant to other classes of anti-HIV-1 agents and earlier integrase strand transfer inhibitors, Cabotegravir showed efficient inhibition of HIV replication through inhibiting HIV integrase. It is an investigational new drug under development for the treatment of HIV infection.
理化性质和储存条件
Molecular Weight (MW)405.35
FormulaC19H17F2N3O5
CAS No.1051375-10-0
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 38 mg/mL (93.7 mM)
Water:<1 mg/mL
Ethanol:<1 mg/mL
SMILES CodeC[C@H]1CO[C@H]2N1C(C3=C(O)C(C(C(NCC4=C(F)C=C(F)C=C4)=O)=CN3C2)=O)=O
Synonyms

GSK744; S/GSK 1265744; GSK-744; S/GSK1265744; GSK 744; S/GSK-1265744; Cabotegravir; Cabenuva.

Chemical Name: (3S,11aR)-N-(2,4-difluorobenzyl)-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide

Exact Mass: 405.1136

实验参考方法
In Vitro

In vitro activity: GSK1265744 inhibits HIV replication with EC50 of 0.22 nM and 0.34-1.3 nM against HIV-1 Ba-L and NL432, respectively. GSK1265744 produces cytotoxicity with CC50 of 6.4, 5.0, 9.2, and 13 μM in proliferating IM-9, U-937, MT-4, and Molt-4 cell lines, respectively.


Kinase Assay: The inhibitory concentrations of GSK1265744 is measured in a strand transfer assay using recombinant HIV IN. A complex of integrase and biotinylated donor DNA–streptavidin-coated SPA beads is formed by incubating 2 μM purified recombinant integrase with 0.66 μM biotinylated donor DNA–4 mg/mL streptavidin-coated SPA beads in 25 mM sodium MOPS pH 7.2, 23 mM NaCl, and 10 mM MgCl2 for 5 minutes at 37°C. These beads are spun down and preincubated with diluted INSTIs for 60 minutes at 37°C. Next, [3H]-labeled target DNA substrate is added to give a final concentration of 7 nM substrate, and the strand transfer reaction is incubated at 37°C for 25 to 45 minutes, which allowed for a linear increase in strand transfer of donor DNA to radiolabeled target DNA. The signal is read using a Wallac MicroBeta scintillation plate reader.


Cell Assay: Using resistance passage experiments, integrase enzyme assays, and cellular assays with site-directed molecular (SDM) HIV clones resistant to other classes of anti-HIV-1 agents and earlier integrase strand transfer inhibitors, results showed that GSK1265744 efficiently inhibited HIV replication through inhibiting HIV integrase

In VivoGSK1265744 (50 mg/kg) treatment protects rhesus macaques against three high-dose SHIV challenges.
Animal modelIn female pigtail macaques model that intravaginal inoculated simian/human immunodeficiency virus twice a week for up to 11 weeks, GSK744 injection prevented the macaques from being infected by virus while placebo controls were infected after a 4 median vaginal challenges with SHIV which reminded that GSK744 may be a potential preexposure prophylaxis drug for prevention via inhibiting HIV integrase
Formulation & Dosage
References

Antimicrob Agents Chemother. 2015 Jan;59(1):397-406; Sci Transl Med. 2015 Jan 14;7(270):270ra4.