BI-9564 - Epigenetic Reader Domain 抑制劑 - 生命科學試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBI-9564Cat. No.: HY-100352CAS No.: 1883429-22-8分式: CHNO分量: 353.41作靶點: Epigenetic Reader Domain作通路: 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 : 7.2 mg/mL (20.37 mM; Need warmi

2、ng)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.8296 mL 14.1479 mL 28.2957 mL5 mM 0.5659 mL 2.8296 mL 5.6591 mL10 mM 0.2830 mL 1.4148 mL 2.8296 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。BIOLOGICAL ACTIVITY物活性 BI-9564種選擇性的，細胞透過的 BRD9 BD 抑制劑，對 BRD9 的 Kd 值為 5.9 nM，對 BET 家族的 IC50 值 100 M。IC5

3、0 & Target Kd: 20 nM (BRD9)體外研究BI-9564 (40% is observed for only 2 out of 55 GPCRs. BI-9564 has antiproliferative effect on human acutemyeloid eosinophilic leukemia cell line EOL-1, with EC50 of 800 nM 1. BI-9564 shows Kd of 73 nM for1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEBRD7, and is 10-f

4、old more selective for BRD9 over the highly homologues bromodomain BRD7, which hasbeen implied as a tumor suppressor and is down-regulated in cancer cells 2.體內(nèi)研究 BI-9564 (180 mg/kg, p.o.) shows attractive ADME/PK profiles for in vivo proof-of-concept studies. BI-9564results in a modest but significa

5、nt additional survival benefit of 2 days compared to survival of the controlgroup in a xenograft model of human AML 1.PROTOCOLCell Assay 1 Cells are grown in 50 L medium as specified by the supplier for 7 days starting with 500 and with 1000 cellsper well of a 384 well plate in the presence of varyi

6、ng concentrations of compound before measuring viabilityvia cellular ATP levels using the cell titer glow assay.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Female CIEA-NOG mice are engrafted intravenously with 1107 EOL-1 AML cells stably expr

7、essingAdministration 1 luciferase and GFP. Following injection of the cells animals are randomized based on body weight(n=10/group). Treatment starts on day 5 with either 0.5% Natrosol or BI-9564 formulated with 0.5% Natrosol.All doses are calculated relative to the mouse body weight on the treatmen

8、t day. BI-9564 and the vehiclecontrol are administered orally with a dosing volume of 10 mL/kg body weight. BI-9564 is administered dailyfrom day 5 until 17 and from day 20 until 22. Dosing is interrupted on day 18 for two days as one mouse inthe treatment group reaches -15% body weight loss. Tumour

9、 load is measured 2-3 times weekly based onbioluminescence imaging. The following scoring system is used: score 0, no clinical signs; score 1, tail orhind limb weakness. Animals are sacrificed based on severity criteria including appearance of paralysis score1 and/or body weight loss exceeding -18%.

10、 In S54 this tumor mouse model body weight changes can occurdue to increased tumor load or due to intolerability.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Martin LJ, et al. Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. J Med Chem. 2016 May 26;59(10):4462-75.2. Rezaul M. Karim, et al. An Advanced Tool To Interrogate BRD9. J. Med. Chem., 2016, 59 (10), pp 4459-4461McePdfHeightCaution: Product has not been fu