1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEA-485Cat. No.: HY-107455CAS No.: 1889279-16-6分式: CHFNO分量: 536.48作靶點: Epigenetic Reader Domain; Histone Acetyltransferase作通路: Epigenetics儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數據體外實驗 DMSO : 100 m

2、g/mL (186.40 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.8640 mL 9.3200 mL 18.6400 mL5 mM 0.3728 mL 1.8640 mL 3.7280 mL10 mM 0.1864 mL 0.9320 mL 1.8640 mL請根據產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。體內實驗 請根據您的實驗動物和給藥式選擇適當的溶解案，配制前請先配制澄清的儲備液，再依次添加助溶劑(為保證實驗結果的可靠性，體內實驗的作液，建議您

3、現現配，當天使；澄清的儲備液可以根據儲存條件，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: 3.5 mg/mL (6.52 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 3.5 mg/mL (6.52 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility:

4、 3.5 mg/mL (6.52 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 A-485p300/CBP 的強效選擇性催化抑制劑，對 p300 和 CBP 組蛋酰轉移酶 (HAT) 的 IC50 值分別為 9.8nM 和 2.6 nM。IC50 & Target IC50: 9.8 nM (p300), 2.6 nM (CBP) 1體外研究 A three-hour treatment of prostate adenocarcinoma PC-3 cell

5、s with A-485 results in a dose-dependentdecrease in H3K27Ac, with a half maximal effective concentration (EC50) of 73 nM. Treatment with A-485does not alter p300 or CBP protein levels. The broadest sensitivity is observed in haematological tumours,where A-485 exhibits potent activity in most multipl

6、e myeloma cell lines, and in a subset of acute myeloidleukaemia lines and non-Hodgkins lymphoma lines. A-485 induces a comparable decrease in H3K27Ac in allfive prostate cancer cell lines 1.體內研究 After tumours are established in SCID male mice, twice daily intraperitoneal injections of A-485 induce 5

7、4%tumour growth inhibition after 21 days of dosing (PMYC and the AR-dependent gene SLC45A3 at threehours post-dosing, and (for MYC) a decrease in the protein level, indicating that A-485 inhibits p300-mediated transcriptional activity in vivo. However, at 16hours post-dosing on the seventh day, A-48

8、5 druglevels in the plasma and tumour are decreased as compare to 3hours. A-485 induces a moderate 9% bodyweight loss, and the animals recover rapidly upon completion of the A-485 dosing regimen 1.PROTOCOLCell Assay 1 Cell lines are plated in 96 well or 384 well plates and allowed to adhere for 24 h

9、. The cells are then treatedwith A-485 for 3, 4, or 5 days. Experiments are run in triplicate and the fraction of viable cells is determinedusing the Cell Viability Assay according to the manufacturers recommendations. For Thymidine incorporationassays, cells are treated with A-485 for 1, 2, 3, or 4

10、 days. Twenty four hours prior to the time point, tritiatedthymidine is added and cells are incubated for an additional 24 h. Genomic DNA is then isolated on filterplates 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal The LuCap-77 CR prostate

11、PDX model is used in this study. Donor tumors are dissociated and injected as aAdministration 1 brie (1:2) into the right flank of 16 week old male C.B.-17 SCID mice on day 0 in a volume of 0.2 mL. Tumorsare size matched on day 26 post-inoculation with a mean tumor volume of 2113 (SEM) mm3 with dosi

12、ngbeginning on day 28. Mice are randomized into treatment groups using Studylog software based on tumorvolume. LuCap-77 CR xenograft tumors are established in SCID mice and animals are dosed with A-485 asfor 7 days. Three hours post the final dose, tumors are harvested and snap frozen on dry ice 1.M

13、CE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Lasko LM, et al. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours. Nature. 2017 Oct2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE5;550(7674):128-132.McePdfH