ATM/ATR

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研究领域

抑制剂选择性比较

特异性亚型抑制剂

ATM/ATR产品

所有产品 ATM/ATR抑制剂(19) ATM/ATR激活剂(1)

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。	Cell, 2019, 36(2):179-193 Cancer Cell, 2019, 35(5):752-766 Cancer Cell, 2019, 36(2):179-193	Three-dimensional responses of MCF7/IGF-1R cells to TAM (1 μM), E2 and IGF-1. Compared to parental MCF7 cells (a), MCF7/IGF-1R cells (b) in three-dimensional (3D) culture formed bigger acini in response to IGF-1 stimulation and displayed significant TAM resistance when treated with TAM (1 μM) + E2 + IGF-1, which was removable by kinase inhibitors BMS-536924, U0126 and BEZ235 (c). Cells (10,000/well) were seeded in 96-well plates. Acini were formed on 100% Matrigel and cultured for 14 days in starving medium containing 2% Matrigel and 5% charcoal/dextran-stripped fetal bovine serum with the treatments as indicated. Concentrations used: TAM (1 μM), E2 (1 nM) and IGF-1 (100 ng/mL). Confocal image original magnification, × 20. Red, rhodamine phalloidin (actin). Blue, Hoechst blue stain. Results are representative of two individual experiments.
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。	Cell, 2019, 178(2):361-373 Cancer Cell, 2019, 35(5):752-766 Mol Cell, 2019, 74(4):651-663.e8	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。	Cell, 2019, 176(3):505-519 Cancer Res, 2019, 79(1):99-113 Cell Death Differ, 2019, 10.1038/s41418-019-0393-7
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, 2019, 10.1038/s41586-019-1607-3 Nature, 2019, 574(7777):268-272 Cancer Cell, 2019, 35(5):752-766	Western blot for γH2AX in H460 cells treated with Cr(VI) in the presence of a second set of inhibitors (ATM-i2—10 uM KU55933, DNAPK-i2—10 uM NU7441, ATR-i2—10 uM VE821). “γH2AX-total” numbers indicate a total normalized intensity of both γH2AX bands from 2 Western blots.
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。	Cell, 2019, 176(6):1379-1392 Nat Cell Biol, 2019, 21(2):226-237 Theranostics, 2019, 9(15):4375-4390	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.
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。	Nat Commun, 2019, 10(1):1444 Nat Commun, 2019, 10(1):1515 Biomol Ther, 2019, 27(1):34-40	U2OS cells were plated in six-well plates using complete medium. The next day the cells were washed four times with NaCl/P_i before maintaining them for 6 h in serum- and glucose-free DMEM supplemented as indicated in the absence or presence of 0.1 uM Torin 2 for the last 1 h. The cells were control- treated, treated with 1 ug/mL insulin or treated with 1 mM H2O2 for 15 min. Thereafter, cell lysates were prepared and western blotting was performed using the indicated antibodies.
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。	Cell, 2019, 36(2):179-193 Cancer Cell, 2019, 36(2):179-193 Mol Cells, 2019, 42(3):210-217
S7102	Berzosertib (VE-822\|VX970\|M6620) VE-822是一种ATR抑制剂，在HT29细胞中IC50 为 19 nM。	Cell, 2019, 176(1-2):144-153 Mol Cell, 2019, 73(1):22-35.e6 Cancer Res, 2019, 79(19):4855-4868	Western blot analysis of scr or siPNUTS transfected cells without IR or 6 h after 10 Gy. VE-822 was added for 2, 5, 15, 30 or 60 min to indicated samples 6 h after 10 Gy.
S8050	ETP-46464 ETP-46464是一种有效的，选择性ATR抑制剂，IC50为25 nM。	Cell, 2016, 167(5):1264-1280
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, 2019, 176(3):505-519 Nucleic Acids Res, 2019, 10.1093/nar/gkz518 Cell, 2018, 174(5):1127-1142	(B) SAHA treatment impairs the HR capacity of GBM03 cells. AZ20(ATRi) as a positive control.
S8556	AZ31 AZ31是一种选择性的ATM抑制剂，IC50小于0.0012 μM。它具有良好的选择性，对ATM的选择性比对DNA-PK和PI3Kα高500倍，比对mTOR、PI3Kβ和PI3Kγ的选择性高1000倍。
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。	Nature, 2019, 10.1038/s41586-019-1607-3 Nature, 2019, 574(7777):268-272 Mol Cell, 2019, 74(6):1123-1137	Number of γH2AX foci per cell of irradiated (2 Gy) SAS cells treated with inhibitors against ATM (ATMi, KU55933), DNA-PK (DNA-PKi, KU57788), or ATR (ATRi, AZD6738) with or without LY364947.
S8729	AZ32 AZ32是ATM kinase的特异性抑制剂，在小鼠中具有良好的血脑屏障通透性，对ATM酶的IC5值小于0.0062 μM。它具有充分的选择性和高细胞透性。
S8680	AZD1390 AZD1390是一种具有口服活性的、能穿透中枢神经系统的ATM抑制剂，在细胞中IC50为0.78 nM。它对ATM的选择性是对PIKK家族其他相关酶的10,000以上，具有良好的选择性。	Cell Death Differ, 2019, 10.1038/s41418-019-0393-7
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。	Inflammation, 2017, 40(6):1903-1911
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。	Aging, 2018, 10(4):549-560 DNA Repair, 2018, 70:67-71 Mol Cell Biol, 2017, 37(20)	Wildtype bone marrow-derived macrophages (BMDMs) were incubated with and without the MRN complex inhibitor mirin (administered dose of 100 μM) for 2 hours, then were treated with PM (100 μg/mL) for an additional 24 hours. (A) The relative levels of Cxcl1, Cxcl2 and Ifn-γ mRNA transcripts were determined using quantitative PCR. (B) The protein levels of Cxcl1, Cxcl2 and Ifn-γ in the culture supernatants were measured using ELISA. Data are presented as means ± SEMs across at least 3 independent experiments. p < 0.05; *p < 0.01.
S8666	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。	Nucleic Acids Res, 2019, 10.1093/nar/gkz518
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。	Mol Cell, 2019, 74(3):571-583 Oncogene, 2019, 38(14):2451-2463 Mol Cancer Ther, 2019, 10.1158/1535-7163.MCT-19-0474
S4157	Chloroquine diphosphate Chloroquine diphosphate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。	EMBO Mol Med, 2019, 11(10):e9930 Cell Mol Immunol, 2019, 10.1038/s41423-019-0236-y Int J Cancer, 2019, 10.1002/ijc.32395	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.

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。	Cell,2019, 36(2):179-193 Cancer Cell,2019, 35(5):752-766 Cancer Cell,2019, 36(2):179-193	Three-dimensional responses of MCF7/IGF-1R cells to TAM (1 μM), E2 and IGF-1. Compared to parental MCF7 cells (a), MCF7/IGF-1R cells (b) in three-dimensional (3D) culture formed bigger acini in response to IGF-1 stimulation and displayed significant TAM resistance when treated with TAM (1 μM) + E2 + IGF-1, which was removable by kinase inhibitors BMS-536924, U0126 and BEZ235 (c). Cells (10,000/well) were seeded in 96-well plates. Acini were formed on 100% Matrigel and cultured for 14 days in starving medium containing 2% Matrigel and 5% charcoal/dextran-stripped fetal bovine serum with the treatments as indicated. Concentrations used: TAM (1 μM), E2 (1 nM) and IGF-1 (100 ng/mL). Confocal image original magnification, × 20. Red, rhodamine phalloidin (actin). Blue, Hoechst blue stain. Results are representative of two individual experiments.
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。	Cell,2019, 178(2):361-373 Cancer Cell,2019, 35(5):752-766 Mol Cell,2019, 74(4):651-663.e8	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。	Cell,2019, 176(3):505-519 Cancer Res,2019, 79(1):99-113 Cell Death Differ,2019, 10.1038/s41418-019-0393-7
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,2019, 10.1038/s41586-019-1607-3 Nature,2019, 574(7777):268-272 Cancer Cell,2019, 35(5):752-766	Western blot for γH2AX in H460 cells treated with Cr(VI) in the presence of a second set of inhibitors (ATM-i2—10 uM KU55933, DNAPK-i2—10 uM NU7441, ATR-i2—10 uM VE821). “γH2AX-total” numbers indicate a total normalized intensity of both γH2AX bands from 2 Western blots.
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。	Cell,2019, 176(6):1379-1392 Nat Cell Biol,2019, 21(2):226-237 Theranostics,2019, 9(15):4375-4390	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.
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。	Nat Commun,2019, 10(1):1444 Nat Commun,2019, 10(1):1515 Biomol Ther,2019, 27(1):34-40	U2OS cells were plated in six-well plates using complete medium. The next day the cells were washed four times with NaCl/P_i before maintaining them for 6 h in serum- and glucose-free DMEM supplemented as indicated in the absence or presence of 0.1 uM Torin 2 for the last 1 h. The cells were control- treated, treated with 1 ug/mL insulin or treated with 1 mM H2O2 for 15 min. Thereafter, cell lysates were prepared and western blotting was performed using the indicated antibodies.
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。	Cell,2019, 36(2):179-193 Cancer Cell,2019, 36(2):179-193 Mol Cells,2019, 42(3):210-217
S7102	Berzosertib (VE-822\|VX970\|M6620) VE-822是一种ATR抑制剂，在HT29细胞中IC50 为 19 nM。	Cell,2019, 176(1-2):144-153 Mol Cell,2019, 73(1):22-35.e6 Cancer Res,2019, 79(19):4855-4868	Western blot analysis of scr or siPNUTS transfected cells without IR or 6 h after 10 Gy. VE-822 was added for 2, 5, 15, 30 or 60 min to indicated samples 6 h after 10 Gy.
S8050	ETP-46464 ETP-46464是一种有效的，选择性ATR抑制剂，IC50为25 nM。	Cell,2016, 167(5):1264-1280
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,2019, 176(3):505-519 Nucleic Acids Res,2019, 10.1093/nar/gkz518 Cell,2018, 174(5):1127-1142	(B) SAHA treatment impairs the HR capacity of GBM03 cells. AZ20(ATRi) as a positive control.
S8556	AZ31 AZ31是一种选择性的ATM抑制剂，IC50小于0.0012 μM。它具有良好的选择性，对ATM的选择性比对DNA-PK和PI3Kα高500倍，比对mTOR、PI3Kβ和PI3Kγ的选择性高1000倍。
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。	Nature,2019, 10.1038/s41586-019-1607-3 Nature,2019, 574(7777):268-272 Mol Cell,2019, 74(6):1123-1137	Number of γH2AX foci per cell of irradiated (2 Gy) SAS cells treated with inhibitors against ATM (ATMi, KU55933), DNA-PK (DNA-PKi, KU57788), or ATR (ATRi, AZD6738) with or without LY364947.
S8729	AZ32 AZ32是ATM kinase的特异性抑制剂，在小鼠中具有良好的血脑屏障通透性，对ATM酶的IC5值小于0.0062 μM。它具有充分的选择性和高细胞透性。
S8680	AZD1390 AZD1390是一种具有口服活性的、能穿透中枢神经系统的ATM抑制剂，在细胞中IC50为0.78 nM。它对ATM的选择性是对PIKK家族其他相关酶的10,000以上，具有良好的选择性。	Cell Death Differ,2019, 10.1038/s41418-019-0393-7
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。	Inflammation,2017, 40(6):1903-1911
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。	Aging,2018, 10(4):549-560 DNA Repair,2018, 70:67-71 Mol Cell Biol,2017, 37(20)	Wildtype bone marrow-derived macrophages (BMDMs) were incubated with and without the MRN complex inhibitor mirin (administered dose of 100 μM) for 2 hours, then were treated with PM (100 μg/mL) for an additional 24 hours. (A) The relative levels of Cxcl1, Cxcl2 and Ifn-γ mRNA transcripts were determined using quantitative PCR. (B) The protein levels of Cxcl1, Cxcl2 and Ifn-γ in the culture supernatants were measured using ELISA. Data are presented as means ± SEMs across at least 3 independent experiments. p < 0.05; *p < 0.01.
S8666	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。	Nucleic Acids Res,2019, 10.1093/nar/gkz518
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。	Mol Cell,2019, 74(3):571-583 Oncogene,2019, 38(14):2451-2463 Mol Cancer Ther,2019, 10.1158/1535-7163.MCT-19-0474

产品目录	产品描述	文献引用	实验数据
S4157	Chloroquine diphosphate Chloroquine diphosphate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。	EMBO Mol Med, 2019, 11(10):e9930 Cell Mol Immunol, 2019, 10.1038/s41423-019-0236-y Int J Cancer, 2019, 10.1002/ijc.32395	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.

产品目录

产品描述

文献引用

实验数据

S4157