ATM
ATM is a serine/threonine protein kinase and a crucial nexus for the cellular response to DNA double-stranded breaks[1]. Mechanistically, ATM signals to cell-cycle and DNA-repair components by phosphorylating downstream targets including p53, CHK2, NBS1, and BRCA1[2]. Transcription- and topoisomerase I-induced DNA double-strand breaks also activate ATM in post-mitotic neurons and lymphocytes, linking ATM signaling to transcription-associated genome stress[3]. In disease context, ATM mutations cause ataxia-telangiectasia, which includes neurodegeneration, immune dysfunction, radiosensitivity, and cancer predisposition[1]. Compared with related PIKK isoforms, ATM, ATR, and DNA-PK jointly control the DNA damage response, but ATR and DNA-PK can compensate for ATM absence in ataxia-telangiectasia[4]. DNA-PK differs functionally because DNA-PKcs and Ku are essential for double-strand break repair through non-homologous end joining[5]. For experimental applications, loss or inhibition of ATM activity increases sensitivity to ionizing radiation and chemotherapeutic agents that elicit DNA double-strand breaks[2]. KU55933 sensitized cells to the topoisomerase IIα inhibitor NK314, supporting ATM inhibition as a tool for studying DNA repair-dependent drug response[6].
References:
- [1]. McKinnon PJ. ATM and ataxia telangiectasia. EMBO Rep. 2004 Aug;5(8):772-6. doi: 10.1038/sj.embor.7400210. PMID: 15289825; PMCID: PMC1299121. et al. ATM and ataxia telangiectasia. EMBO Rep. 2004 Aug;5(8):772-6. [Content Brief]
- [2]. Harnor S, et al. Modulation of the DNA-Damage Response by Inhibitors of the Phosphatidylinositol 3-Kinase Related Kinase (PIKK) Family[M]//Cancer II. Cham: Springer International Publishing, 2017: 189-189.
- [3]. Sordet O, et al. Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks. EMBO Rep. 2009 Aug;10(8):887-93. [Content Brief]
- [4]. Schlam-Babayov S, et al. It takes three to the DNA damage response tango. Mol Cell Oncol. 2021 Feb 8;8(2):1881395. [Content Brief]
- [5]. Matsumoto Y, et al. DNA-Dependent Protein Kinase Catalytic Subunit: The Sensor for DNA Double-Strand Breaks Structurally and Functionally Related to Ataxia Telangiectasia Mutated. Genes (Basel). 2021 Jul 27;12(8):1143. [Content Brief]
- [6]. Guo L, et al. DNA-dependent protein kinase and ataxia telangiectasia mutated (ATM) promote cell survival in response to NK314, a topoisomerase IIα inhibitor. Mol Pharmacol. 2011 Aug;80(2):321-7. [Content Brief]
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ATM Related Products (34)
Related Products (34)
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Antibodies (3)
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ATR/PARP1-IN-1
0 ImagesCat. No.: HY-174828ATR/PARP1-IN-1 is a potent ATR and PARP1 dual inhibitor with IC50s of 17.3 nM and 0.38 nM, respectively. ATR/PARP1-IN-1 effectively reduces cell viability, induces apoptosis and DNA damage. ATR/PARP1-IN-1 significantly impairs triple-negative breast cancer (TNBC) colony formation, migration, and invasion. ATR/PARP1-IN-1 suppresses tumor growth effectively in MDA-MB-468 xenografted mice, with no significant body weight change.
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ATM Inhibitor-7
0 ImagesCat. No.: HY-149291CAS No.: 3033712-80-7
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ATM Inhibitor-4
0 ImagesCat. No.: HY-144687CAS No.: 2769140-74-9
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AZD-7648 (GMP)
0 ImagesCat. No.: HY-111783GCAS No.: 2230820-11-6AZD-7648 (GMP) is AZD-7648 (HY-111783) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. AZD-7648 is a potent, orally active, selective DNA-PK inhibitor with an IC50 of 0.6 nM. AZD-7648 induces apoptosis and shows antitumor activity.
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ATM Inhibitor-11
0 ImagesCat. No.: HY-169310CAS No.: 2878473-51-7ATM Inhibitor-11 (Compound 1) is an inhibitor for ATM with an IC50 of 0.32 nM. ATM Inhibitor-11 inhibits the KAP1 phosphorylation with an IC50 of 0.97 nM. ATM Inhibitor-11 exhibits high exposure in the brain, heart and plasma of ICR mouse. ATM Inhibitor-11 exhibits anti-tumor efficacy in NCI-H441 xenograft mouse model.
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ATM Inhibitor-2
0 ImagesCat. No.: HY-144685CAS No.: 2769140-29-4
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ATR-IN-20
0 ImagesCat. No.: HY-151915CAS No.: 3012609-63-8ATR-IN-20 is a potent ATR (ATM/ATR) inhibitor with an IC50 of 3 nM. ATR-IN-20 possess an inhibitory effect on mTOR (IC50 of 18 nM) while displaying good selectivity against PI3Kα (100 nM), ATM (100 nM), and DNA-PK (662 nM). ATR-IN-20 exhibits excellent pharmacokinetic profile (F = 30%), and has anticancer effects.
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Antitumor agent-28
0 ImagesCat. No.: HY-141478CAS No.: 2097499-67-5
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Berzosertib hydrochloride
0 ImagesSynonyms: VE-822 hydrochloride; VX-970 hydrochloride; M6620 hydrochlorideBerzosertib (VE-822) hydrochloride is an orally active, CNS-penetrant, and selective ATR kinase inhibitor. Berzosertib hydrochloride blocks ATR kinase activity, abrogates G2/M cell cycle checkpoint, impairs DNA damage repair. Berzosertib hydrochloride induces apoptosis, inhibnits conlony migration, inhibits cell proliferation, and activates cGAS-STING axes in cancer cells. Berzosertib hydrochloride can be used for the research of cancers, such as head and neck squamous cell carcinoma, and colorectal cancer.
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ATM-IN-2
0 ImagesCat. No.: HY-174989ATM-IN-2 is a selective and orally active ATM inhibitor with an IC50 of 4 nM. ATM-IN-2 exhibits excellent kinase selectivity (>700-fold over PIKK family members). ATM-IN-2 exerts its anti-tumor effect by inhibiting ATM phosphorylation and the downstream signaling pathways (p53, H2AX), and promotes cell apoptosis. ATM-IN-2 can be used for the study of chemosensitizer candidate such as colon cancer.
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Americanin A
0 ImagesCat. No.: HY-N18301CAS No.: 69506-79-2Americanin A is a Neolignan. Americanin A can be isolated from the seeds of Phytolacca americana. Americanin A activates ATM and ATR, initiating the subsequent signal transduction cascades that include Chk1, Chk2, and tumor suppressor p53. Americanin A targets selectively Skp2 for degradation and thereby stabilizes p27. Americanin A suppresses the activity of Cyclin B1 and its partner cdc2 to prevent entry into Mitosis. Americanin A induces Apoptosis by producing excessive ROS. Americanin A has anti-cancer activity against colorectal cancer.
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ATM ligand-1
0 ImagesCat. No.: HY-185575CAS No.: 3056059-49-2ATM ligand-1 is an ATM ligand that can be used for the synthesis of PROTACs, such as PROTAC ATM degrader-1 (HY-158345).
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Elrelesertib (Standard)
0 ImagesCat. No.: HY-109566RCAS No.: 2089288-03-7Synonyms: AZD1390 (Standard)Elrelesertib (Standard) (AZD1390 (Standard)) is the analytical standard of Elrelesertib (AZD1390) (HY-109566). This product is intended for research and analytical applications. Elrelesertib (AZD1390) is an orally active, brain-penetrant ATM kinase inhibitor with IC50 values of 0.78 nM. Elrelesertib blocks ATM-dependent DNA damage response, inhibits ATM autophosphorylation and downstream Chk2, Rad50 phosphorylation, and accumulates at DNA breaks. Elrelesertib acts as a radiosensitizer, induces apoptosis, genomic instability, G2-M cell cycle arrest, ROS elevation, and mitochondrial membrane potential alteration. Elrelesertib has low efflux liability against P-gp and BCRP. Elrelesertib can be used for the research of central nervous system malignancies, glioblastoma multiforme, glioma, lung cancer brain metastases, and breast cancer.
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