S/GSK1349572
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
S/GSK1349572(dolutegravir)是一种新型有效的人类免疫缺陷病毒(HIV)整合酶(IN)抑制剂,阻断病毒基因组与宿主细胞DNA整合的链转移。S/GSK1349572占据整合体(intasome)IN活性位点的物理空间,与催化核心域的β4-α2环接触,通过其扩展的连接区连接金属螯合核心的卤代苄基,从而进入病毒DNA腾空的口袋。在外周血单核细胞中,S/GSK1349572具有强烈的抗HIV活性,IC50值为0.51 nM。S/GSK1349572对raltegravir和elvitegravir抗性的HIV仍具有活性。
参考文献:
Sherene Min, Ivy Song, Julie Borland, Shuguang Chen, Yu Lou, Tamio Fujiwara, and Stephen C. Piscitelli. Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 2010; 54(1): 254-258
Masanori Kobayashi, Tomokazu Yoshinaga, Takahiro Seki, Chiaki Wakasa-Morimoto, Kevin W. Brown, Robert Ferris, Scott A. Foster, Richard J. Hazen, Shigeru Miki, Akemi Suyama-Kagitani, Shinobu Kawauchi-Miki, Teruhiko Taishi, Takashi Kawasuji, Brian A. Johns, Mark R. Underwood, Edward P. Garvey, Akihiko Sato, and Tamio Fujiwara. In vitro antiretroviral prooerties of S/GSK1349572, a next-generation HIV integrase inhibitor. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 2011; 55(2): 813-821
Stephen Harem Steven J. Smith, Mathieu Metifiot, Albert Jaxa-Chamiec, Yves Pommier, Stephen H. Hughes, and Peter Cherepanov. Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol Pharmacol 2011; 80(4): 565-572
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 419.4 |
Cas No. | 1051375-16-6 |
Formula | C20H19F2N3O5 |
Synonyms | S/GSK1349572, GSK-1349572 |
Solubility | ≥41.9 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
Chemical Name | (4R,12aS)-N-[(2,4-difluorophenyl)methyl]-7-hydroxy-4-methyl-6,8-dioxo-3,4,12,12a-tetrahydro-2H-pyrido[5,6]pyrazino[2,6-b][1,3]oxazine-9-carboxamide |
SDF | Download SDF |
Canonical SMILES | CC1CCOC2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)O |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
激酶实验[1]: | |
抑制活性 |
使用重组HIV整合酶的链转移实验测量S/GSK1349572的抑制效力。通过将2 μM纯化的重组整合酶、0.66 μM生物素化供体DNA-4mg/ml链霉亲和素包被的SPA磁珠在25 mM吗啉丙磺酸钠(MOPS)(pH 7.2)、23 mMNaCl和10 mM MgCl2中37℃孵育5分钟,形成整合酶和生物素化的预处理的供体DNA-链霉素包被的Acintillation proximity assay (SPA)复合体。将这些磁珠离心并在37℃下用稀释的S/GSK1349572预培养60分钟。然后加入3H-标记的靶DNA底物以得到终浓度为7 nM的底物,将链转移反应混合物在37℃温育25至45分钟,使供体DNA的链转移到放射性标记的靶DNA线性增加。使用WallacMicroBeta闪烁板读数器读取信号。 |
细胞实验 [1]: | |
细胞系 |
HIV-1毒株IIIB感染的MT-4细胞,PBMC。 |
溶解方法 |
该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月 |
反应条件 |
0.16、0.8、4、20 nM,4或5 天. |
实验结果 |
在MT-4细胞中,S/GSK1349572抑制HIV-1,EC50值为0.71 nM。此外,在PBMC和PHIV实验中,S/GSK1349572抑制HIV-1,其EC50值分别为0.51和2.2 nM。在增殖性IM-9、U-937、MT-4和Molt-4细胞中,S/GSK1349572的50%细胞毒性浓度(CC50)分别为4.8、7.0、14和15 μM。在用HIV-1 NL432感染的MT-4细胞中,S/GSK1349572抑制病毒复制。 |
动物实验[2]: | |
动物模型 |
C57BL/6 小鼠 |
剂量 |
2.7 mg/kg/day,两周,口服 |
实验结果 |
在C57BL/6小鼠中,S/GSK1349572显著增加血清肌酐,这与竞争性抑制肌酐分泌的整合酶抑制剂一致。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
References: [1]. Kobayashi M, Yoshinaga T, Seki T, et al. In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother, 2011, 55(2): 813-821. [2]. Eadon MT, Zhang H, Skaar TC, et al. A two-week regimen of high-dose integrase inhibitors does not cause nephrotoxicity in mice. AntivirChemChemother, 2015 |
描述 | Dolutegravir (GSK1349572)是双金属结合HIV整合酶抑制剂,IC50值为2.7 nM。 | |||||
靶点 | HIV integrase | |||||
IC50 | 2.7 nM |
质量控制和MSDS
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