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Literature summary extracted from

  • Rozpedek, W.; Pytel, D.; Nowak-Zdunczyk, A.; Lewko, D.; Wojtczak, R.; Diehl, J.; Majsterek, I.
    Breaking the DNA damage response via serine/threonine kinase inhibitors to improve cancer treatment (2019), Curr. Med. Chem., 26, 1425-1445 .
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.7.11.1 additional information ATR is activated upon range spectrum of DNA damage agents involving UV light, alkylating agents, chemical inhibitors of DNA replication machinery as well as other pathological conditions that cause DNA single-strand breaks Homo sapiens
2.7.11.1 additional information the enzyme (ATM) is activated in response to DNA double-strand breaks especially caused via gamma irradiation Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.11.1 AZD-6738 ATR inhibition sensitizes cancer cells to ionizing radiation and chemotherapeutics agents (cisplatin, carboplatin, gemcitabine and bendamustine) Homo sapiens
2.7.11.1 Caffeine ATM/ATR inhibition sensitizes cancer cells to ionizing radiation, nonspecific inhibitor for ATM and ATR; ATM/ATR inhibition sensitizes cancer cells to ionizing radiation, nonspecific inhibitor for ATM and ATR Homo sapiens
2.7.11.1 CP466722 enzyme (ATM) inhibition sensitizes cancer cells to ionizing radiation, evokes defects in cell cycle checkpoints Homo sapiens
2.7.11.1 ETP-46464 ATR inhibition, sensitizes cancer cells to ionizing radiation and chemotherapeutics agents non-specific inhibitor for ATR Homo sapiens
2.7.11.1 GSK2606414 PERK inhibition. Inhibition of PERKdependent, pro-adaptive unfolded protein response signaling pathway Homo sapiens
2.7.11.1 GSK2656157 PERK inhibition. Inhibition of PERKdependent, pro-adaptive unfolded protein response signaling pathway Homo sapiens
2.7.11.1 KU-55933 enzyme (ATM) inhibition sensitizes cancer cells to ionizing radiation and DNA DSBs inducing chemotherapeutics agents Homo sapiens
2.7.11.1 KU-59403 enzyme (ATM) inhibition significant chemosensitization and radiosensitization Homo sapiens
2.7.11.1 KU-60019 enzyme (ATM) inhibition sensitizes cancer cells to ionizing radiation Homo sapiens
2.7.11.1 LY294002 enzyme (ATM) inhibition sensitizes cancer cells to ionizing radiation, non-specific inhibitor for ATM Homo sapiens
2.7.11.1 NU6027 ATR inhibition, sensitizes cancer cells to ionizing radiation and chemotherapeutics agents non-specific inhibitor for ATR Homo sapiens
2.7.11.1 NVP-BEZ235 ATR inhibition, sensitizes cancer cells to ionizing radiation and chemotherapeutics agents non-specific inhibitor for ATR Homo sapiens
2.7.11.1 Torin 2 ATR inhibition, sensitizes cancer cells to ionizing radiation and chemotherapeutics agents non-specific inhibitor for ATR Homo sapiens
2.7.11.1 VE-821 ATR inhibition, sensitizes cancer cells to ionizing radiation and chemotherapeutics agents, blocks activation of Chk1-dependent signaling pathway, enhances DNA damage in combination with cisplatin, arrests cell cycle in G2/M phase Homo sapiens
2.7.11.1 VE-822 ATR inhibition sensitizes cancer cells to ionizing radiation and chemotherapeutics agents (cisplatin, oxaliplatin, gemcitabine, etoposide and SN38, the active metabolite of irinotecan) Homo sapiens
2.7.11.1 Wortmannin enzyme (ATM) inhibition sensitizes cancer cells to ionizing radiation Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.11.1 ATP + L-seryl-[Eukaryotic initiation factor 2] Homo sapiens
-
 ADP + H+ + O-phospho-L-seryl-[Eukaryotic initiation factor 2]
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.11.1 Homo sapiens Q13315
-
-
2.7.11.1 Homo sapiens Q13535
-
-
2.7.11.1 Homo sapiens Q9NZJ5
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.11.1 ATP + L-seryl-[Eukaryotic initiation factor 2]
-
 Homo sapiens ADP + H+ + O-phospho-L-seryl-[Eukaryotic initiation factor 2]
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.11.1 Ataxia-telangiectasia and Rad3-Related
-
 Homo sapiens
2.7.11.1 ataxia-telangiectasia mutated
-
 Homo sapiens
2.7.11.1 ATM
-
 Homo sapiens
2.7.11.1 ATR
-
 Homo sapiens
2.7.11.1 PERK
-
 Homo sapiens
2.7.11.1 serine/threonine protein kinase R (PKR)-like endoplasmic reticulum kinase
-
 Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.7.11.1 0.000074
-
 pH and temperature not specified in the publication Homo sapiens AZD-6738
2.7.11.1 0.0004
-
 pH and temperature not specified in the publication Homo sapiens GSK2606414
2.7.11.1 0.0009
-
 pH and temperature not specified in the publication Homo sapiens GSK2656157

General Information

EC Number General Information Comment Organism
2.7.11.1 physiological function serine/threonine kinases such as Ataxia-telangiectasia and Rad3-Related (ATR) is a major regulators of DNA damage response, since after sensing stalled DNA replication forks, DNA double- or single-strand breaks, it may directly phosphorylate and activate its downstream targets, that play a key role in DNA repair, cell cycle arrest and apoptotic cell death. Activated ATR phosphorylated substrates play a vital role during the inhibition of cell cycle progression. They are also essential for upregulation of DNA damage response genes Homo sapiens
2.7.11.1 physiological function serine/threonine kinases such as Ataxia-telangiectasia mutated (ATM) is a major regulators of DNA damage response, since after sensing stalled DNA replication forks, DNA double- or single-strand breaks, it may directly phosphorylate and activate its downstream targets, that play a key role in DNA repair, cell cycle arrest and apoptotic cell death. Activated ATM phosphorylated substrates play a vital role during the inhibition of cell cycle progression. They are also essential for upregulation of DNA damage response genes Homo sapiens
2.7.11.1 physiological function the enzyme is directly associated with cancer development and progression. PERK is an essential serine/threonine kinase that has a significant influence on cell cycle regulation. Due to the fact that PERK links ER stress with cell cycle progression it constitutes a key mediator of checkpoint essential for re-establish a cellular homeostasis Homo sapiens