ATM/ATR

信号通路图

研究领域

抑制剂选择性比较
溶解性比较

目录号	产品目录	溶解度(25°C)
目录号	产品目录	水	DMSO	酒精
S1009	Dactolisib (BEZ235, NVP-BEZ235)	<1 mg/mL	0.01 mg/mL	<1 mg/mL
S1092	KU-55933 (ATM Kinase Inhibitor)	<1 mg/mL	33 mg/mL	<1 mg/mL
S1570	KU-60019	<1 mg/mL	18 mg/mL	<1 mg/mL
S8007	VE-821	<1 mg/mL	74 mg/mL	<1 mg/mL
S2758	Wortmannin	<1 mg/mL	85 mg/mL	<1 mg/mL
S8729	AZ32	<1 mg/mL	66 mg/mL	7 mg/mL
S8680	AZD1390	<1 mg/mL	14 mg/mL	95 mg/mL
S8666	BAY 1895344 (BAY-1895344)	82 mg/mL	82 mg/mL	82 mg/mL
S2817	Torin 2	<1 mg/mL	20 mg/mL	<1 mg/mL
S2245	CP-466722	<1 mg/mL	0.28 mg/mL	<1 mg/mL
S7102	VE-822	<1 mg/mL	36 mg/mL	<1 mg/mL
S8050	ETP-46464	<1 mg/mL	6 mg/mL	<1 mg/mL
S7136	CGK 733	<1 mg/mL	100 mg/mL	<1 mg/mL
S7050	AZ20	<1 mg/mL	83 mg/mL	3 mg/mL
S7693	AZD6738	<1 mg/mL	82 mg/mL	41 mg/mL
S3600	Schisandrin B (Sch B)	<1 mg/mL	80 mg/mL	10 mg/mL
S8096	Mirin	<1 mg/mL	44 mg/mL	<1 mg/mL
S8375	AZD0156	<1 mg/mL	0.3 mg/mL	2 mg/mL
S4157	Chloroquine Phosphate	100 mg/mL	<1 mg/mL	<1 mg/mL

特异性亚型抑制剂

ATM/ATR抑制剂（19）
新ATM/ATR产品

产品目录	产品描述	文献引用	实验数据
S1009	Dactolisib (BEZ235, NVP-BEZ235) Dactolisib (BEZ235, NVP-BEZ235) 是一种双重ATP竞争性 PI3K 和 mTOR 抑制剂，在无细胞试验中，抑制 p110α/γ/δ/β 和 mTOR(p70S6K) 的 IC50 分别为 4 nM /5 nM /7 nM /75 nM /6 nM。在 3T3^TopBP1-ER 细胞中抑制 ATR，IC50 为 21 nM，而对 Akt 和 PDK1 的抑制作用很弱。Phase 2。	Nature, 2018, 560(7718):372-376 Nature, 2017, 543(7647):728-732 Nature, 2012, 487(7408):505-9	Level of phospho-proteins in RTK and PI3K–Akt–mTOR pathways in treated tumours, detected with western blot.
S1092	KU-55933 (ATM Kinase Inhibitor) KU-55933 (ATM Kinase Inhibitor)是一种有效的，特异性ATM抑制剂，在无细胞试验中IC50/K_i为12.9 nM/2.2 nM，与DNA-PK， PI3K/PI4K， ATR和mTOR相比，对ATM具有高度选择性。	Nature, 2018, 560(7716):112-116 Nature, 2015, 528(7582):422-6 Nature, 2015, 10.1038/nature14328	Effects of NVP-BKM120 and KU-55933 and their combination on the DNA damage response. A, HCC1937 cells were treated for 18 hours with NVP-BKM120 at 2.5 μmol/L, KU-55933 at 10 μmol/L, or their combination, subjected to ionizing radiation(IR) with 10 Gy or mock, lysed 6 hours later, and subjected to immunoblotting with antibodies as indicated.
S1570	KU-60019 KU-60019是一种改进的KU-55933类似物，在无细胞试验中作用于ATM，IC50为6.3 nM，作用于ATM比作用于DNA-PK和ATR的选择性分别高270和1600倍，并且是高度有效的放射增敏剂。	Nat Commun, 2016, 7:13701 Int J Cancer, 2013, 135(2):479-91 Int J Cancer, 2015, 136(6):1445-57	The ATM-dependent Ser15-p53 phosphorylation was monitored by Western blotting. Protein loading levels were monitored by probing for actin.
S8007	VE-821 VE-821是一种有效的，选择性的，ATP竞争性ATR抑制剂，在无细胞试验中K_i/IC50为13 nM/26 nM，抑制H2AX磷酸化，对PIKKs ATM， DNA-PK， mTOR和PI3Kγ具有很低的抑制活性。	Nature, 2018, 555(7696):387-391 Nature, 2016, 539(7627):54-58 Nature, 2015, 518(7538):254-7	Cell viability response to ATR inhibitor.
S2758	Wortmannin Wortmannin是一种首次命名的PI3K抑制剂，在无细胞试验中IC50为3 nM，对 PI3K 家族的选择性较低。也会抑制自噬体的形成，并有效抑制DNA-PK/ATM，在无细胞试验中IC50为16 nM和150 nM。	Nature, 2015, 10.1038/nature14412 Science, 2016, 353(6302):929-32 Cancer Res, 2014, 74(10):2846-56	L3.6pl cells at 6,000 cells per well were incubated in MEM with 5% FBS in triplicate in a 96-well culture plate and then treated alone with 5 umol/L BMS-777607, 10 umol/L wortmannin, or with BMS-777607 in combination with individual inhibitors. Polyploidy was examined under BK71 Olympus microscope and photographed 72 hours after treatment.
S8729^New	AZ32 AZ32 is a specific inhibitor of the ATM kinase that possesses good BBB penetration in mouse with an IC50 value of <0.0062 μM for ATM enzyme. It shows adequate selectivity over ATR and also has high cell permeability.
S8680^New	AZD1390 AZD1390 is a first-in-class orally available and CNS penetrant ATM inhibitor with an IC50 of 0.78 nM in cells and >10,000-fold selectivity over closely related members of the PIKK family of enzymes and excellent selectivity across a broad panel of kinases.
S8666^New	BAY 1895344 (BAY-1895344) BAY 1895344是有效的、高选择性的、具有口服生物活性的ATR抑制剂，IC50为7 nM。
S2817	Torin 2 Torin 2 是一种有效的选择性mTOR抑制剂，在p53−/− MEFs细胞系中IC50为0.25 nM；作用于mTOR比作用于PI3K选择性高800倍，并且改善了药代动力学性能。抑制ATM/ATR/DNA-PK，在PC3细胞系中EC50分别为28 nM/35 nM/118 nM。	J Clin Invest, 2013, 124(2):742-54 Cell Rep, 2015, 11(3):446-59 Arterioscler Thromb Vasc Biol, 2018, 10.1161/ATVBAHA.118.311321	Immunofluorescent imaging of HAECs using VE-CAD (red) and p120 (green) antibodies was performed 12 h after DMSO (control), Torin-2 (100 nM), or EVL (500 nM) treatments. White arrows denote interendothelial gaps. White bar indicates 50 μm. EVL treatment increased VE-CAD mobilization from the membrane into the cytosol (relative to DMSO) with evidence of intracellular deposits and interendothelial gaps, whereas in DMSO-treated cells, there was colocalization of p120 and VE-CAD (yellow border) with no evidence of gap formation. In Torin-2-treated cells, there was evidence of colocalization of p120 and VE-CAD at cell borders with minimal interendothelial gap formation.
S2245	CP-466722 CP-466722是一种有效的，可逆的ATM抑制剂，不影响ATR，且抑制PI3K或PIKK家族成员。	PLoS One, 2012, 7(11):e50423 PLoS One, 2015, 10(7):e0134411 J Neurooncol, 2012, 110(3):349-57	HCT116 cells expressing the DDR-Act reporter were treated with Etoposide 20 μM (E20) for 24 hours, in the absence or in the presence of KU-55933 or CP-466722 at the indicated concentration. (A) Western blot analysis of p53 and actin as control.
S7102	VE-822 VE-822是一种ATR抑制剂，在HT29细胞中IC50 为 19 nM。	Mol Cancer Ther, 2018, 17(7):1504-1514 J Virol, 2015, 10.1128/JVI.00389-15 Am J Cancer Res, 2018, 8(7):1307-1316	Flow cytometry analysis of E14.5 FL lineage negative cells from indicated genotypes treated with ATMi (KU-55933; 1nM), ATRi (VE-822; 1nM) or both inhibitors or DMSO as a negative control for 24 hours in culture before AnnexinV and PI levels were measured.
S8050	ETP-46464 ETP-46464是一种有效的，选择性ATR抑制剂，IC50为25 nM。
S7136	CGK 733 CGK 733是一种有效的ATM/ATR选择性抑制剂，IC50约为200 nM。	Mol Cells, 2016, 39(12):869-876	K562 and K562R cells were pre-treated for 1 h with CGK733 (5 μM), then treated with CTD (10 μM) for 24 h, and protein levels of cleaved PARP, Mcl-1, and phosphorylated H3 were determined by Western blotting. GAPDH served as a normal control.
S7050	AZ20 AZ20是一种新型有效的选择性ATR激酶抑制剂，无细胞试验中IC50为5 nM，比作用于mTOR的选择性高8倍。	Cell, 2018, 174(5):1127-1142 Mol Oncol, 2016, 10(5):751-63 Sci Rep, 2017, 7:41950	(B) SAHA treatment impairs the HR capacity of GBM03 cells. AZ20(ATRi) as a positive control.
S7693	AZD6738 AZD6738是一种口服具有活性的，选择性 ATR 激酶抑制剂，IC50 为 1 nM。Phase 1/2。	Clin Cancer Res, 2018, 10.1158/1078-0432.CCR-18-1346 J Exp Clin Cancer Res, 2018, 37(1):205 Am J Cancer Res, 2018, 8(7):1307-1316	AZD6738 (AZD) synergizes with cytarabine (ara-C) to induce apoptosis and proliferation inhibition in AML cells. (a) OCI-AML3 cells were treated with cytarabine and AZD6738, alone or in combination, for 24 h and then subjected to annexin V-FITC/PI staining and flow cytometry analyses. CI values were calculated using CompuSyn software. Combined drug treatments were compared to single drug treatment using 1-way ANOVA with Bonferroni post hoc test. ***indicates p < 0.001. (b and c) OCI-AML3 cells were treated with cytarabine and AZD-6738, alone or in combination, for 24 h. Whole cell lysates were subjected to Western blotting and probed with the indicated antibodies.
S3600	Schisandrin B (Sch B) Schisandrin B (Sch B)是中草药五味子(Turcz.)中含量最丰富的二苯并环辛二烯木酚素。它是一种安全的ATR和P-gp抑制剂。
S8096	Mirin Mirin是有效的Mre11–Rad50–Nbs1（MRN）复合体抑制剂，能够抑制Mre11相关的外切酶活性。
S8375	AZD0156 AZD0156是有效的、选择性的ATM激酶抑制剂，具有潜在的化疗/辐射增敏和抗肿瘤活性。
S4157	Chloroquine Phosphate Chloroquine Phosphate是一种4-氨基喹啉的抗疟疾和抗风湿药，也是一种ATM激活剂。	Leukemia, 2017, 10.1038/leu.2016.325 Cell Signal, 2016, 28(8):1086-98 Int J Mol Med, 2017, 10.3892/ijmm.2017.3008	NCI-H929 EV and miR-137 OE cells were treated with ATM activator Chloroquine Phosphate (CQ), specific ATM inhibitor KU-55933, and ATR inhibitor AZ20 for 12 hr. Immunoblotting showed the expression of p-ATM, p-Chk2, p-BRCA1, p-ATR and p-Chk1.

研究领域

产品类型

ATM/ATR

信号通路图

研究领域

特异性亚型抑制剂