S1009 |
Dactolisib (BEZ235)
|
Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3TopBP1-ER cell. Dactolisib induces autophagy and suppresses HIV-1 replication. Phase 2. |
-
Nat Cell Biol, 2024, 10.1038/s41556-024-01473-0
-
J Clin Invest, 2024, 134(18)e179860
-
Haematologica, 2024, 109(6):1713-1725
|
|
S1092 |
KU-55933
|
KU-55933 is a potent and specific ATM inhibitor with IC50/Ki of 12.9 nM/2.2 nM in cell-free assays, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR. KU‑55933 (ATM Kinase Inhibitor) inhibits the activation of autophagy‑initiating kinase ULK1 and results in a significant decrease of autophagy. |
-
Nature, 2024, 629(8011):443-449
-
Nature, 2024, 629(8011):443-449
-
Cell, 2024, 187(20):5698-5718.e26
|
|
S2758 |
Wortmannin
|
Wortmannin is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Wortmannin blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays. Wortmannin also inhibits PLK1 activity. |
-
Nature, 2024, 10.1038/s41586-024-07990-0
-
Nat Commun, 2024, 15(1):451
-
Nat Commun, 2024, 15(1):4926
|
|
S8007 |
VE-821
|
VE-821(ATR inhibitor IV) is a potent and selective ATP competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM in cell-free assays, shows inhibition of H2AX phosphorylation, minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ. |
-
Cell, 2024, 187(14):3652-3670.e40
-
Nat Commun, 2024, 15(1):4667
-
Nat Commun, 2024, 15(1):2089
|
|
S4157 |
Chloroquine diphosphate
|
Chloroquine diphosphate is a 4-aminoquinoline anti-malarial and anti-rheumatoid agent, also acting as an ATM activator. Chloroquine is also an inhibitor of toll-like receptors (TLRs). |
-
Nat Commun, 2024, 15(1):1642
-
Cancer Lett, 2024, 604:217258
-
Phytomedicine, 2024, 135:156053
|
|
S1570 |
KU-60019
|
KU-60019 is an improved analogue of KU-55933, with IC50 of 6.3 nM for ATM in cell-free assays, 270- and 1600-fold more selective for ATM than DNA-PK and ATR,and is a highly effective radiosensitizer. |
-
Cell Death Dis, 2024, 15(7):519
-
Cell Rep, 2024, 43(5):114205
-
Mol Biol Cell, 2024, 35(8):br15
|
|
S7102 |
Berzosertib (VE-822)
|
Berzosertib (VE-822, VX970, M6620) is an ATR inhibitor with IC50 of 19 nM in HT29 cells. |
-
Cell, 2024, 187(20):5698-5718.e26
-
Nat Commun, 2024, 15(1):6517
-
Mol Cell, 2024, S1097-2765(24)00285-5
|
|
S7693 |
Ceralasertib (AZD6738)
|
Ceralasertib (AZD6738) is an orally active, and selective ATR kinase inhibitor with IC50 of 1 nM. Phase 1/2.
|
-
Nat Struct Mol Biol, 2024, 10.1038/s41594-024-01279-6
-
Nat Commun, 2024, 15(1):4430
-
J Exp Clin Cancer Res, 2024, 43(1):77
|
|
S2817 |
Torin 2
|
Torin 2 is a potent and selective mTOR inhibitor with IC50 of 0.25 nM in p53−/− MEFs cell line; 800-fold greater selectivity for mTOR than PI3K and improved pharmacokinetic properties. Inhibition of ATM/ATR/DNA-PK with EC50 of 28 nM/35 nM/118 nM,in PC3 cell lines respectively. Torin 2 decreases cell viability and induces autophagy and apoptosis. |
-
Nat Commun, 2024, 15(1):7675
-
Microorganisms, 2024, 12(2)296
-
Autophagy, 2023, 19(11):2912-2933
|
|
S7050 |
AZ20
|
AZ20 is a novel potent and selective inhibitor of ATR kinase with IC50 of 5 nM in a cell-free assay, 8-fold selectivity over mTOR. |
-
EMBO J, 2024, 10.1038/s44318-024-00111-7
-
bioRxiv, 2024, 2024.06.24.600514
-
Nucleic Acids Res, 2023, 51(19):10467-10483
|
|
S8375 |
AZD0156
|
AZD0156 is a potent and selective inhibitors of ATM kinase, with potential chemo-/radio-sensitizing and antineoplastic activities. AZD0156 prevents DNA damage checkpoint activation, disrupts DNA damage repair, induces tumor cell apoptosis, and leads to cell death of ATM-overexpressing tumor cells. |
-
Cell, 2024, S0092-8674(24)00963-2
-
Nat Commun, 2024, 15(1):7404
-
Cancers (Basel), 2024, 16(8)1510
|
|
S8096 |
Mirin
|
Mirin is a potent Mre11–Rad50–Nbs1 (MRN) complex inhibitor, and inhibits Mre11-associated exonuclease activity. Mirin inhibits MRN-dependent activation of ATM. |
-
Nat Commun, 2024, 15(1):6197
-
Mol Cell, 2024, S1097-2765(24)00285-5
-
Nucleic Acids Res, 2024, gkae721
|
|
S8680 |
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. |
-
Nature, 2024, 629(8011):443-449
-
Nature, 2024, 629(8011):443-449
-
Cell Rep, 2024, 43(3):113896
|
|
S2245 |
CP-466722
|
CP-466722 is a potent and reversible ATM inhibitor, does not affect ATR and inhibits PI3K or PIKK family members in cells. |
-
G3 (Bethesda), 2020, 4;10(5):1585-1597
-
Cell, 2019, 36(2):179-193
-
Cancer Cell, 2019, 36(2):179-193
|
|
S8666 |
Elimusertib (BAY-1895344) hydrochloride
|
Elimusertib (BAY-1895344) hydrochloride is a potent, highly selective and orally available ATR inhibitor with an IC50 of 7 nM. |
-
Cell Death Dis, 2023, 14(6):348
-
Cell Death Dis, 2023, 14(6):348
-
Cell Rep, 2023, 42(4):112296
|
|
S8050 |
ETP-46464
|
ETP-46464 is a potent and selective inhibitor of ATR with IC50 of 25 nM. |
-
mBio, 2024, e0228723.
-
iScience, 2023, 25(7)
-
Cell Rep, 2022, 41(11):111836
|
|
S7136 |
CGK 733
|
CGK 733 is a potent and selective inhibitor of ATM/ATR with IC50 of ~200 nM. |
-
Exp Cell Res, 2022, S0014-4827(22)00218-X
-
Aging (Albany NY), 2021, 13(8):11705-11726
-
mBio, 2020, 11(1)
|
|
S9864 |
Elimusertib (BAY-1895344)
|
Elimusertib (BAY-1895344) is a very potent and highly selective ATR (ataxia telangiectasia and Rad3-related) inhibitor with IC50 of 7 nM. Elimusertib potently inhibits proliferation of a broad spectrum of human tumor cell lines with median IC50 of 78 nM. |
-
bioRxiv, 2024, 2024.05.03.592420
-
Neurooncol Adv, 2024, 6(1):vdad165
-
Cancer Chemother Pharmacol, 2023, 92(1):57-69
|
|
S9639 |
VX-803 (M4344)
|
VX-803 (M4344, ATR inhibitor 2) is an ATP-competitive, orally active, and selective inhibitor of ataxia telangiectasia and Rad3 related (ATR) kinase with Ki of < 150 pM. VX-803 (M4344) potently inhibits ATR-driven phosphorylated checkpoint kinase-1 (P-Chk1) phosphorylation with IC50 of 8 nM. VX-803 (M4344) exhibits potential antineoplastic activity. |
-
bioRxiv, 2024,
-
bioRxiv, 2024, 2024.06.24.600514
-
Viruses, 2023, 15(5)1112
|
|
S8556 |
AZ31
|
AZ31 is a selective and novel ATM inhibitor with an IC50 of <0.0012 μM. It shows excellent selectivity over closely related enzymes (>500 fold selective over DNA-PK and PI3Kα and >1000 fold selective over mTOR, PI3Kβ and PI3Kγ). |
-
Proc Natl Acad Sci U S A, 2020, 117(50):31891-31901
|
|
S8729 |
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. |
-
Cancers (Basel), 2022, 14(20)4984
|
|
S0148 |
HAMNO
|
HAMNO (NSC-111847) is a potent and selective replication protein A (RPA) inhibitor with anti-tumor activity. HAMNO inhibits both ATR autophosphorylation and phosphorylation of RPA32 Ser33 by ATR. |
-
mBio, 2023, e0352822.
|
|
E1411 |
Tuvusertib
|
Tuvusertib (M1774, ATR inhibitor 1) is a potent ATR inhibitor, which exhibits anti-proliferative and anti-tumor effects in cancer cell lines. |
|
|
S3224 |
Cinobufagin
|
Cinobufagin (Cinobufagine), an active ingredient of Venenum Bufonis, inhibits tumor development. Cinobufagin increases ATM and Chk2 and decreases CDC25C, CDK1, and cyclin B. Cinobufagin inhibits PI3K, AKT and Bcl-2 while increases levels of cleaved caspase-9 and caspase-3. Thus, Cinobufagin induces cell cycle arrest at the G2/M phase and apoptosis. |
|
|
E1108 |
Camonsertib (RP-3500)
|
Camonsertib (RP-3500) is a highly potent and selective inhibitor of ATR kinase with an IC50 of 1 nM. |
|
|
S3600 |
Schisandrin B
|
Schisandrin B is the most abundant dibenzocyclooctadiene lignan present in the traditional Chinese medicinal herb Schisandra chinensis (Turcz.) Baill. It is a kind of ATR and P-gp inhibitor with high safety. |
-
Drug Des Devel Ther, 2024, 18:4241-4256
-
Viruses, 2022, 14(2)353
-
Pharmacol Res, 2021, 166:105459
|
|
S6885 |
Ailanthone
|
Ailanthone (AIL, Δ13-Dehydrochaparrinone), a natural anti-hepatocellular carcinoma (HCC) component in Ailanthus altissima, induces G0/G1-phase cell cycle arrest by decreasing expression of cyclins and CDKs and increases expression of p21 and p27. Ailanthone triggers DNA damage characterized by activation of the ATM/ATR pathway. Ailanthone induces apoptosis which is mitochondrion-mediated and involves the PI3K/AKT signaling pathway in Huh7 cells. Ailanthone is also a potent inhibitor of both full-length Androgen Receptor (AR-FL) and constitutively active truncated AR splice variants (AR-Vs, AR1-651) with IC50 of 69 nM and 309 nM, respectively. |
-
Theranostics, 2024, 14(4):1371-1389
|
|
E1057 |
Lartesertib (M4076)
|
Lartesertib (M4076) inhibits Ataxia telangiectasia-mutated (ATM) kinase activity with a sub-nanomolar potency and shows remarkable selectivity against other protein kinases, suppresses DSB repair, clonogenic cancer cell growth, and potentiates antitumor activity of ionizing radiation in cancer cell lines. |
|
|
E1989New |
ART0380
|
ART0380 (IACS-030380) is a potent and selective, orally bioavailable inhibitor of ATR kinase, with an IC50 of 51.7 nM effectively inhibiting the enzyme activity of the ATR-ATRIP complex. It functions as an ATP-competitive inhibitor, binding to the ATP pocket of ATR, where ATP would typically bind. It interacts with the hinge through its morpholine oxygen and occupies the ribose pocket with a sulfoximine group. It also exhibits antitumor activity. |
|
|
E1136 |
SKLB-197
|
SKLB-197 exerts selectively inhibition against ataxia telangiectasia mutated and Rad3-related (ATR) kinase with IC50 of 0.013 μM, also displays potent antitumor activity against ATM-deficent tumors both in vitro and in vivo. |
|
|
E1512New |
M3541
|
M3541 is a potent and selective inhibitor of ATM kinase activity with an IC50 value of 0.25 nM in cell-free assays. M3541 suppresses double-strand breaks (DSB) repair, clonogenic cancer cell growth and potentiates antitumor activity of ionizing radiation in cancer cell lines. |
|
|
S1009 |
Dactolisib (BEZ235)
|
Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3TopBP1-ER cell. Dactolisib induces autophagy and suppresses HIV-1 replication. Phase 2. |
- Nat Cell Biol, 2024, 10.1038/s41556-024-01473-0
- J Clin Invest, 2024, 134(18)e179860
- Haematologica, 2024, 109(6):1713-1725
|
|
S1092 |
KU-55933
|
KU-55933 is a potent and specific ATM inhibitor with IC50/Ki of 12.9 nM/2.2 nM in cell-free assays, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR. KU‑55933 (ATM Kinase Inhibitor) inhibits the activation of autophagy‑initiating kinase ULK1 and results in a significant decrease of autophagy. |
- Nature, 2024, 629(8011):443-449
- Nature, 2024, 629(8011):443-449
- Cell, 2024, 187(20):5698-5718.e26
|
|
S2758 |
Wortmannin
|
Wortmannin is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Wortmannin blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays. Wortmannin also inhibits PLK1 activity. |
- Nature, 2024, 10.1038/s41586-024-07990-0
- Nat Commun, 2024, 15(1):451
- Nat Commun, 2024, 15(1):4926
|
|
S8007 |
VE-821
|
VE-821(ATR inhibitor IV) is a potent and selective ATP competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM in cell-free assays, shows inhibition of H2AX phosphorylation, minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ. |
- Cell, 2024, 187(14):3652-3670.e40
- Nat Commun, 2024, 15(1):4667
- Nat Commun, 2024, 15(1):2089
|
|
S1570 |
KU-60019
|
KU-60019 is an improved analogue of KU-55933, with IC50 of 6.3 nM for ATM in cell-free assays, 270- and 1600-fold more selective for ATM than DNA-PK and ATR,and is a highly effective radiosensitizer. |
- Cell Death Dis, 2024, 15(7):519
- Cell Rep, 2024, 43(5):114205
- Mol Biol Cell, 2024, 35(8):br15
|
|
S7102 |
Berzosertib (VE-822)
|
Berzosertib (VE-822, VX970, M6620) is an ATR inhibitor with IC50 of 19 nM in HT29 cells. |
- Cell, 2024, 187(20):5698-5718.e26
- Nat Commun, 2024, 15(1):6517
- Mol Cell, 2024, S1097-2765(24)00285-5
|
|
S7693 |
Ceralasertib (AZD6738)
|
Ceralasertib (AZD6738) is an orally active, and selective ATR kinase inhibitor with IC50 of 1 nM. Phase 1/2.
|
- Nat Struct Mol Biol, 2024, 10.1038/s41594-024-01279-6
- Nat Commun, 2024, 15(1):4430
- J Exp Clin Cancer Res, 2024, 43(1):77
|
|
S2817 |
Torin 2
|
Torin 2 is a potent and selective mTOR inhibitor with IC50 of 0.25 nM in p53−/− MEFs cell line; 800-fold greater selectivity for mTOR than PI3K and improved pharmacokinetic properties. Inhibition of ATM/ATR/DNA-PK with EC50 of 28 nM/35 nM/118 nM,in PC3 cell lines respectively. Torin 2 decreases cell viability and induces autophagy and apoptosis. |
- Nat Commun, 2024, 15(1):7675
- Microorganisms, 2024, 12(2)296
- Autophagy, 2023, 19(11):2912-2933
|
|
S7050 |
AZ20
|
AZ20 is a novel potent and selective inhibitor of ATR kinase with IC50 of 5 nM in a cell-free assay, 8-fold selectivity over mTOR. |
- EMBO J, 2024, 10.1038/s44318-024-00111-7
- bioRxiv, 2024, 2024.06.24.600514
- Nucleic Acids Res, 2023, 51(19):10467-10483
|
|
S8375 |
AZD0156
|
AZD0156 is a potent and selective inhibitors of ATM kinase, with potential chemo-/radio-sensitizing and antineoplastic activities. AZD0156 prevents DNA damage checkpoint activation, disrupts DNA damage repair, induces tumor cell apoptosis, and leads to cell death of ATM-overexpressing tumor cells. |
- Cell, 2024, S0092-8674(24)00963-2
- Nat Commun, 2024, 15(1):7404
- Cancers (Basel), 2024, 16(8)1510
|
|
S8096 |
Mirin
|
Mirin is a potent Mre11–Rad50–Nbs1 (MRN) complex inhibitor, and inhibits Mre11-associated exonuclease activity. Mirin inhibits MRN-dependent activation of ATM. |
- Nat Commun, 2024, 15(1):6197
- Mol Cell, 2024, S1097-2765(24)00285-5
- Nucleic Acids Res, 2024, gkae721
|
|
S8680 |
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. |
- Nature, 2024, 629(8011):443-449
- Nature, 2024, 629(8011):443-449
- Cell Rep, 2024, 43(3):113896
|
|
S2245 |
CP-466722
|
CP-466722 is a potent and reversible ATM inhibitor, does not affect ATR and inhibits PI3K or PIKK family members in cells. |
- G3 (Bethesda), 2020, 4;10(5):1585-1597
- Cell, 2019, 36(2):179-193
- Cancer Cell, 2019, 36(2):179-193
|
|
S8666 |
Elimusertib (BAY-1895344) hydrochloride
|
Elimusertib (BAY-1895344) hydrochloride is a potent, highly selective and orally available ATR inhibitor with an IC50 of 7 nM. |
- Cell Death Dis, 2023, 14(6):348
- Cell Death Dis, 2023, 14(6):348
- Cell Rep, 2023, 42(4):112296
|
|
S8050 |
ETP-46464
|
ETP-46464 is a potent and selective inhibitor of ATR with IC50 of 25 nM. |
- mBio, 2024, e0228723.
- iScience, 2023, 25(7)
- Cell Rep, 2022, 41(11):111836
|
|
S7136 |
CGK 733
|
CGK 733 is a potent and selective inhibitor of ATM/ATR with IC50 of ~200 nM. |
- Exp Cell Res, 2022, S0014-4827(22)00218-X
- Aging (Albany NY), 2021, 13(8):11705-11726
- mBio, 2020, 11(1)
|
|
S9864 |
Elimusertib (BAY-1895344)
|
Elimusertib (BAY-1895344) is a very potent and highly selective ATR (ataxia telangiectasia and Rad3-related) inhibitor with IC50 of 7 nM. Elimusertib potently inhibits proliferation of a broad spectrum of human tumor cell lines with median IC50 of 78 nM. |
- bioRxiv, 2024, 2024.05.03.592420
- Neurooncol Adv, 2024, 6(1):vdad165
- Cancer Chemother Pharmacol, 2023, 92(1):57-69
|
|
S9639 |
VX-803 (M4344)
|
VX-803 (M4344, ATR inhibitor 2) is an ATP-competitive, orally active, and selective inhibitor of ataxia telangiectasia and Rad3 related (ATR) kinase with Ki of < 150 pM. VX-803 (M4344) potently inhibits ATR-driven phosphorylated checkpoint kinase-1 (P-Chk1) phosphorylation with IC50 of 8 nM. VX-803 (M4344) exhibits potential antineoplastic activity. |
- bioRxiv, 2024,
- bioRxiv, 2024, 2024.06.24.600514
- Viruses, 2023, 15(5)1112
|
|
S8556 |
AZ31
|
AZ31 is a selective and novel ATM inhibitor with an IC50 of <0.0012 μM. It shows excellent selectivity over closely related enzymes (>500 fold selective over DNA-PK and PI3Kα and >1000 fold selective over mTOR, PI3Kβ and PI3Kγ). |
- Proc Natl Acad Sci U S A, 2020, 117(50):31891-31901
|
|
S8729 |
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. |
- Cancers (Basel), 2022, 14(20)4984
|
|
S0148 |
HAMNO
|
HAMNO (NSC-111847) is a potent and selective replication protein A (RPA) inhibitor with anti-tumor activity. HAMNO inhibits both ATR autophosphorylation and phosphorylation of RPA32 Ser33 by ATR. |
- mBio, 2023, e0352822.
|
|
E1411 |
Tuvusertib
|
Tuvusertib (M1774, ATR inhibitor 1) is a potent ATR inhibitor, which exhibits anti-proliferative and anti-tumor effects in cancer cell lines. |
|
|
E1108 |
Camonsertib (RP-3500)
|
Camonsertib (RP-3500) is a highly potent and selective inhibitor of ATR kinase with an IC50 of 1 nM. |
|
|
S3600 |
Schisandrin B
|
Schisandrin B is the most abundant dibenzocyclooctadiene lignan present in the traditional Chinese medicinal herb Schisandra chinensis (Turcz.) Baill. It is a kind of ATR and P-gp inhibitor with high safety. |
- Drug Des Devel Ther, 2024, 18:4241-4256
- Viruses, 2022, 14(2)353
- Pharmacol Res, 2021, 166:105459
|
|
E1057 |
Lartesertib (M4076)
|
Lartesertib (M4076) inhibits Ataxia telangiectasia-mutated (ATM) kinase activity with a sub-nanomolar potency and shows remarkable selectivity against other protein kinases, suppresses DSB repair, clonogenic cancer cell growth, and potentiates antitumor activity of ionizing radiation in cancer cell lines. |
|
|
E1989New |
ART0380
|
ART0380 (IACS-030380) is a potent and selective, orally bioavailable inhibitor of ATR kinase, with an IC50 of 51.7 nM effectively inhibiting the enzyme activity of the ATR-ATRIP complex. It functions as an ATP-competitive inhibitor, binding to the ATP pocket of ATR, where ATP would typically bind. It interacts with the hinge through its morpholine oxygen and occupies the ribose pocket with a sulfoximine group. It also exhibits antitumor activity. |
|
|
E1136 |
SKLB-197
|
SKLB-197 exerts selectively inhibition against ataxia telangiectasia mutated and Rad3-related (ATR) kinase with IC50 of 0.013 μM, also displays potent antitumor activity against ATM-deficent tumors both in vitro and in vivo. |
|
|
E1512New |
M3541
|
M3541 is a potent and selective inhibitor of ATM kinase activity with an IC50 value of 0.25 nM in cell-free assays. M3541 suppresses double-strand breaks (DSB) repair, clonogenic cancer cell growth and potentiates antitumor activity of ionizing radiation in cancer cell lines. |
|
|