Vicriviroc-maleate-SCH-417690-maleate-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEVicriviroc maleateCat. No.: HY-17377CAS No.: 599179-03-0Synonyms: SCH-417690 (maleate); SCH-D (maleate)分式: CHFNO分量: 649.7作靶點: CCR; HIV作通路: GPCR/G Protein; Immunology/Inflammation; Anti-infection儲存式: Powder -20C 3 years4C 2 years

2、In solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (76.96 mM; Need ultrasonic)H2O : 25 mg/mL (38.48 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.5392 mL 7.6959 mL 15.3917 mL5 mM 0.3078 mL 1.5392 mL 3.0783 mL10 mM 0.1539 mL 0.7696 mL 1.5392 mL請根據(jù)產(chǎn)品在不

3、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?，配制前請先配制澄清的儲備液，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)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: 2.5 mg/mL (3.85 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% S

4、BE-CD in saline)Solubility: 2.5 mg/mL (3.85 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (3.85 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Vicriviroc maleate種有效，選擇性，可服，可透過腦屏障的 CCR5 拮抗劑，Ki 值為 2.5 nM，同時抑制外周 單核細胞中的 HIV-1 的活性，

5、IC90 值分別為 3.3 nM (JrFL)，2.8 nM (ADA-M)，1.8 nM (301657)，4.9nM (JV1083) 和 10 nM (RU 570)。IC50 & Target CCR5 HIV-1 (301657) HIV-1 (ADA-M) HIV-1 (JrFL)2.5 nM (Ki) 1.8 nM (IC90, in 2.8 nM (IC90, in 3.3 nM (IC90, inPBMC cells) PBMC cells) PBMC cells)HIV-1 (JV1083) HIV-1 (RU 570)4.9 nM (IC90, in PBMC 10 nM

6、 (IC90, in PBMCcells) cells)體外研究 Vicriviroc (Sch-417690/Sch-D) is a potent, selective and oral bioavailable inhibitor of CCR5, with a Ki of 2.5nM, and also inhibits HIV-1 in PBMC cells, with IC90s of 3.3 (JrFL), 2.8 (ADA-M), 1.8 (301657), 4.9 (JV1083)and 10 nM (RU570). In addition, Vicriviroc shows

7、a mean IC50 and IC90 of 0.45 nM and 4 nM for a panel ofHIV isolates, and has weak activity against hERG activity (IC50, 5.8 M) 1. Vicriviroc inhibits chemotacticresponse to MIP-1 with IC50 values below 1 nM, and suppresses RANTES-induced signaling with a meanIC50 of 4.2 1.3 nM. Vicriviroc potently s

8、uppresses all the viral isolates tested, with geometric mean EC50sof 0.04-2.3 nM and IC90s of 0.45-18 nM 2.體內(nèi)研究 Vicriviroc (10 mg/kg) has good oral availablity in rats and monkeys, with no acute CNS or GI effects in rats1.PROTOCOLCell Assay 2 Ficoll-purified peripheral blood mononuclear cells (PBMCs

9、) are stimulated in vitro with phytohemagglutinin(PHA) (5 g/mL) and interleukin-2 (IL-2) (50 U/mL) for 3 to 7 days. The cells are resuspended at 4 106/mLin complete medium (RPMI, 10% fetal bovine serum FBS, 50 U/mL IL-2), seeded into 96-well plates (2 105/well), incubated with an equal volume of cul

10、ture medium containing compound (Vicriviroc) for 1 h at37C, and infected in triplicate with 25 to 100 50% tissue culture infectious doses (TCID50) per well of viralinoculum for 3 to 4 h. Cells are washed twice in phosphate-buffered saline (PBS) to remove residual virusand are cultured with compound

11、for 4 to 6 days. HIV-1 replication is quantified by measurement ofextracellular p24 antigen in the supernatants by enzyme-linked immunosorbent assay. The 50% effectiveconcentrations (EC50s) and EC90s for each virus are determined using Graphpad PRISM software 2.MCE has not independently confirmed th

12、e accuracy of these methods. They are for reference only.REFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Tagat JR, et al. Piperazine-based CCR5 antagonists as HIV-1 inhibitors. IV. Discovery of 1-(4,6-dimethyl-5-pyrimidinyl)carbonyl- 4-4-2-methoxy-1(R)-4-(trifluoromethyl)phenylethyl-3(

13、S)-methyl-1-piperazinyl- 4-methylpiperidine (Sch-417690/Sch-D), a potent, highlyselective, and orally bioavailable CCR5 antagonist. J Med Chem. 2004 May 6;47(10):2405-8.2. Strizki JM, et al. Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against humanimmunodeficiency virus type 1. Antimicrob Agents Chemother. 2005 Dec;49(12):4911-9.Mce