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Literature summary for 2.7.11.1 extracted from
- Breaking the DNA damage response via serine/threonine kinase inhibitors to improve cancer treatment (2019), Curr. Med. Chem., 26, 1425-1445 .
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| 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 | |
| additional information | the enzyme (ATM) is activated in response to DNA double-strand breaks especially caused via gamma irradiation | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| AZD-6738 | ATR inhibition sensitizes cancer cells to ionizing radiation and chemotherapeutics agents (cisplatin, carboplatin, gemcitabine and bendamustine) | Homo sapiens | |
| 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 |  |
| CP466722 | enzyme (ATM) inhibition sensitizes cancer cells to ionizing radiation, evokes defects in cell cycle checkpoints | Homo sapiens | |
| ETP-46464 | ATR inhibition, sensitizes cancer cells to ionizing radiation and chemotherapeutics agents non-specific inhibitor for ATR | Homo sapiens | |
| GSK2606414 | PERK inhibition. Inhibition of PERKdependent, pro-adaptive unfolded protein response signaling pathway | Homo sapiens | |
| GSK2656157 | PERK inhibition. Inhibition of PERKdependent, pro-adaptive unfolded protein response signaling pathway | Homo sapiens | |
| KU-55933 | enzyme (ATM) inhibition sensitizes cancer cells to ionizing radiation and DNA DSBs inducing chemotherapeutics agents | Homo sapiens | |
| KU-59403 | enzyme (ATM) inhibition significant chemosensitization and radiosensitization | Homo sapiens | |
| KU-60019 | enzyme (ATM) inhibition sensitizes cancer cells to ionizing radiation | Homo sapiens | |
| LY294002 | enzyme (ATM) inhibition sensitizes cancer cells to ionizing radiation, non-specific inhibitor for ATM | Homo sapiens | |
| NU6027 | ATR inhibition, sensitizes cancer cells to ionizing radiation and chemotherapeutics agents non-specific inhibitor for ATR | Homo sapiens | |
| NVP-BEZ235 | ATR inhibition, sensitizes cancer cells to ionizing radiation and chemotherapeutics agents non-specific inhibitor for ATR | Homo sapiens | |
| Torin 2 | ATR inhibition, sensitizes cancer cells to ionizing radiation and chemotherapeutics agents non-specific inhibitor for ATR | Homo sapiens | |
| 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 | |
| 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 | |
| Wortmannin | enzyme (ATM) inhibition sensitizes cancer cells to ionizing radiation | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + L-seryl-[Eukaryotic initiation factor 2] | Homo sapiens | - |
ADP + H+ + O-phospho-L-seryl-[Eukaryotic initiation factor 2] | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q13315 | - |
- |
| Homo sapiens | Q13535 | - |
- |
| Homo sapiens | Q9NZJ5 | - |
- |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + L-seryl-[Eukaryotic initiation factor 2] | - |
Homo sapiens | ADP + H+ + O-phospho-L-seryl-[Eukaryotic initiation factor 2] | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| Ataxia-telangiectasia and Rad3-Related | - |
Homo sapiens |
| ataxia-telangiectasia mutated | - |
Homo sapiens |
| ATM | - |
Homo sapiens |
| ATR | - |
Homo sapiens |
| PERK | - |
Homo sapiens |
| serine/threonine protein kinase R (PKR)-like endoplasmic reticulum kinase | - |
Homo sapiens |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.000074 | - |
pH and temperature not specified in the publication | Homo sapiens | AZD-6738 | |
| 0.0004 | - |
pH and temperature not specified in the publication | Homo sapiens | GSK2606414 | |
| 0.0009 | - |
pH and temperature not specified in the publication | Homo sapiens | GSK2656157 |
General Information
| General Information | Comment | Organism |
|---|---|---|
| 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 |
| 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 |
| 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 |
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