Temsavir-BMS-626529-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETemsavirCat. No.: HY-15440CAS No.: 701213-36-7Synonyms: BMS-626529分式: CHNO分量: 473.48作靶點: HIV作通路: Anti-infection儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 16.67 mg/mL (35.21 mM)* means

2、soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.1120 mL 10.5601 mL 21.1202 mL5 mM 0.4224 mL 2.1120 mL 4.2240 mL10 mM 0.2112 mL 1.0560 mL 2.1120 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍福渲魄罢埾扰渲瞥吻宓膬湟?，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)

3、現(xiàn)配，當天使；澄清的儲備液可以根據(jù)儲存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 1.67 mg/mL (3.53 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 1.67 mg/mL (3.53 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedC

4、hemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 1.67 mg/mL (3.53 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Temsavir (BMS-626529)種 HIV-1 gp120 抑制劑，抑制其結(jié)合到 CD4+ T 細胞。IC50 & Target HIV-1 1體外研究 Temsavir has half-maximal effective concentration (EC50) values of 50 against LAI virus of 0.70.4 nM.Temsavi

5、r exhibits an EC50 of 0.01 nM against the most susceptible virus and an EC50 of 2,000 nM againstthe least susceptible virus. The cytotoxicity profile of Temsavir is examined in several cell types from differenthuman tissues. CC50 values of 200 M are observed in MT-2 (T lymphocytes), HEK293 (kidney),

6、 HEp-2(larynx), HepG2 (liver), HeLa (cervix), HCT116 (colorectal), MCF-7 (breast), SK-N-MC (neuroepithelium),HOS (bone), H292 (lung), and MDBK (bovine kidney) cells measured after 3 or 6 days in culture. CC50values of 105 and 192 M are obtained in the T-cell line PM1 and in PBMCs, respectively, foll

7、owing 6 days inculture. These results show that Temsavir exhibits low cytotoxicity in cell culture 1. Temsavir exhibits abroad spectrum of antiviral activity against a panel of clinical isolates, with a 50% inhibitory concentration(IC50) ranging from subnanomolar levels to 0.1 M 2.PROTOCOLKinase Ass

8、ay 1 Micro BioSpin 6 columns are used to measure the binding of 3HBMS-488043 or 3HTemsavir to gp120.Binding solutions (30 L) containing 25 mM Tris-HCl (pH 7.5), 125 mM NaCl, 50 nM gp120JRFL, and serialdilutions of 3HBMS-488043 or 3HTemsavir are allowed to equilibrate and then adsorbed to a MicroBioS

9、pin6 column. The column is centrifuged (14,000 rpm) for 5 min, the eluent is collected, and radioactivity isdetermined with a scintillation counter. To measure dissociative kinetics, 150 nM 3HTemsavir or 90 nM3HBMS-488043 is incubated with 60 nM gp120 at ambient temperature for 1 h to achieve equili

10、briumbinding, and then a large molar excess (14-fold) of soluble CD4 protein is added to drive dissociation.Aliquots are taken at the indicated time intervals, adsorbed to a spin column, and centrifuged, and theradioactivity in the eluent is quantitated. Comparison of the tritium signal from paralle

11、l samples with andwithout the soluble CD4 challenge allowed for the determination of the percent compound bound 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Cytotoxicity assays are performed in the presence of serially diluted Temsavir

12、 for up to 6 days, and cellviability is quantitated using an XTT assay. To determine CC50 values (concentration of drug required to kill50% of cells), laboratory-adapted peripheral blood mononuclear cells (PBMCs) are initially plated at a densityof 0.1106 cells/mL. In the absence of compounds, the c

13、ell densities typically reach 1106 to 1.2106/mLafter 6 days 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Nowicka-Sans B, et al. In vitro antiviral characteristics of HIV-1 attachment inh

14、ibitor BMS-626529, the active component of the prodrugBMS-663068. Antimicrobial Agents and Chemotherapy (2012), 56(7), 3498-3507.2. Nettles RE, et al. Pharmacodynamics, safety, and pharmacokinetics of BMS-663068, an oral HIV-1 attachment inhibitor in HIV-1-infected subjects. J Infect Dis. 2012 Oct 1;206(7)