貨號	規格	價格	上海	北京	武漢	南京
S87680-1mg	99.86%	￥300.00 S87680-1mg ￥300.00 現貨	5 5	-	-	-
S87680-5mg	99.86%	￥500.00 S87680-5mg ￥500.00 現貨	2 2	-	-	-
S87680-10mg	99.86%	￥980.00 S87680-10mg ￥980.00 現貨	4 4	-	-	-
S87680-25mg	99.86%	￥1950.00 S87680-25mg ￥1950.00 現貨	5 5	-	-	-
S87680-50mg	99.86%	￥3310.00 S87680-50mg ￥3310.00 現貨	1 1	-	-	-

產品介紹

AZD1390 is an exceptionally potent inhibitor of ATM in cells (IC50: 0.78 nM) with >10,000-fold selectivity over closely related members of the PIKK family of enzymes.

產品描述：

AZD1390 is an exceptionally potent inhibitor of ATM in cells (IC50: 0.78 nM) with >10,000-fold selectivity over closely related members of the PIKK family of enzymes.

靶點：

ATM:0.78 nM (cell based);ATM/ATR

體外研究：

ATM autophosphorylation inhibition by AZD1390 occurred at 4 hours after treatment, and 3 nM produced strong inhibition of ATM in LN18 GBM cells. Other DDR inhibitors tested under the same conditions at relevant IC50 concentrations did not affect pATM levels. A dose-dependent increase in G2 accumulation occurred after 24 hours following AZD1390 and irradiation at 2 Gy indicative of cells not arresting in S and accumulating in G2 or experiencing problems during mitosis.

體內研究：

In in vivo syngeneic and patient-derived glioma as well as orthotopic lung-brain metastatic models, AZD1390 dosed in combination with daily fractions of IR (whole-brain or stereotactic radiotherapy) significantly induced tumor regressions and increased animal survival compared to IR treatment alone.

細胞實驗：

Cells were seeded in six-well plates to a density of 50 to 60% and incubated at 37°C for 24 hours. Cells were pretreated with AZD1390, the ATR inhibitor AZD6738, the Wee1 inhibitor AZD1775, the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib, or the DNA-PK inhibitor KU-0060648 at indicated concentrations for 1 hour and subsequently irradiated at 2 Gy using the Faxitron CellRad (130-kV, 5-mA, 0.5-mm Al). In washout experiments, the cell culture medium was immediately replaced and cells were incubated with or without the compound for 1, 6, and 24 hours. In all other experiments, proteins were collected at indicated time points following irradiation. Proteins were harvested by scraping the cells in radioimmunoprecipitation assay (RIPA) lysis buffer supplemented with protease and phosphatase inhibitors. Protein content was quantified using the BCA Protein Assay Kit according to manufacturing conditions. Proteins were separated by SDS–polyacrylamide gel electrophoresis on 4 to 12% bis-tris

動物實驗：

Bioluminescence signaling of implanted 3 × 10^5 NCI-H2228-Luc cells was measured using an IVIS Xenogen imaging machine to monitor tumor growth. When the signal reached the range of 10^7 to 10^8, the mice were randomized into different treatment groups and treated orally with either vehicle or AZD1390 QD or BID + IR at 2.5 Gy daily for four consecutive days. AZD1390 or vehicle was dosed at 1 hour before IR on each dosing day. The bioluminescence signals and body weight of the mice were measured once weekly, and the raw data were recorded according to their study number and measurement date in the in vivo database. TGI from the start of treatment was assessed by comparison of the mean change in bioluminescence intensity for the control and treated groups and presented as % of TGI. The calculation of inhibition and regression was based on the geometric mean of relative tumor volume (RTV) in each group. 'CG' means the geometric mean of RTV of the control group, whereas 'TG' means the geometric mean of RTV of the

參考文獻：

1. Durant ST, et al. The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves survival of preclinical brain tumor models. Sci Adv. 2018 Jun 20;4(6):eaat1719.

溶解性：

Soluble in DMSO

保存條件：

-20°C

配置溶液濃度參考：

	1mg	5mg	10mg
1 mM	2.094 ml	10.47 ml	20.939 ml
5 mM	0.419 ml	2.094 ml	4.188 ml
10 mM	0.209 ml	1.047 ml	2.094 ml
50 mM	0.042 ml	0.209 ml	0.419 ml

注意：

部分產品我司僅能提供部分信息，我司不保證所提供信息的權威性，僅供客戶參考交流研究之用。

參考文獻

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AZD-1390