ARV-771 _BET PROTAC Degrader - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEARV-771Cat. No.: HY-100972CAS No.: 1949837-12-0分式: CHClNOS分量: 986.64作靶點: PROTAC; Epigenetic Reader Domain作通路: PROTAC; Epigenetics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 : 50 mg/mL (50

2、.68 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.0135 mL 5.0677 mL 10.1354 mL5 mM 0.2027 mL 1.0135 mL 2.0271 mL10 mM 0.1014 mL 0.5068 mL 1.0135 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?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結果的可靠

3、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 (2.53 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (2.53 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn o

4、il1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (2.53 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 ARV-771種 PROTAC 類的有效 BET 降解劑。對 BRD2(1)，BRD2(2)，BRD3(1)，BRD3(2)，BRD4(1) 和BRD4(2) 的 Kd 值分別為 34，4.7，8.3，7.6，9.6 和 7.6 nM 1。IC50 & Target BRD2(1) BRD2(2) BRD3(1) BRD3(2)34 nM (Kd) 4.7

5、 nM (Kd) 8.3 nM (Kd) 7.6 nM (Kd)BRD4(1) BRD4(2)9.6 nM (Kd) 7.6 nM (Kd)體外研究 ARV-771, a small-molecule pan-BET degrader based on proteolysis-targeting chimera (PROTAC)technology, demonstrates dramatically improved efficacy in cellular models of CRPC as compared with BETinhibition. ARV-771 potently deg

6、rades BRD2/3/4 in 22Rv1 cells with a DC50 less than 5 nM. c-MYC proteinis a downstream effector of BET proteins. Treatment with ARV-771 results in depletion of c-MYC with anIC50 of less than 1 nM. ARV-771 shows strong antiproliferative effect on 22Rv1, VCaP, and LnCaP95 celllines. ARV-771 treatment

7、has a pronounced effect on cell morphology consistent with apoptosis. FL-AR andAR-V7 mRNA are down-regulated upon treatment with 10 nM ARV-771 in VCaP cells. ARV-771 has anantiandrogenic effect on a number of AR-regulated genes in VCaP cells 1.體內(nèi)研究 Treatment of non castrated male Nu/Nu mice bearing

8、AR-V7+ 22Rv1 tumor xenografts with dailysubcutaneous injections of ARV-771 at 10 mg/kg for 3 d results in 37% and 76% down-regulation of BRD4and c-MYC levels, respectively, in tumor tissue. A marked down-regulation in levels of AR-V7 is observed inthe 22Rv1 tumors after ARV-771 treatment 1.PROTOCOLC

9、ell Assay 1 ARV-771 is dissolved in DMSO. 22Rv1 cells (5,000 cells per well) are dosed with ARV-771 serially diluted1:3 for a 10-point dose curve for 72 h. CellTiter-Glo Luminescent Cell Viability Assay is added, and the plateis read on a luminometer. Data are analyzed and plotted using GraphPad Pri

10、sm software 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Mice bearing tumors are treated with ARV-771 (5, 10, 30, 50 mg/kg) for up to 3 wk, depending on theAdministration 1 experiment. Mice are sacrificed 8 h after the final dose. Plas

11、ma and tissues are harvested and flash frozenfor further analysis 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Clin Cancer Res. 2019 Jun 1;25(11):3404-3416.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Raina K, et al. PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer. Proc Natl Acad Sci U SA. 2016 Jun 28;113(26):7124-9.McePdfHeightCaution: Produc