ATR
Ataxia telangiectasia mutated (ATM) encodes a serine/threonine protein kinase that coordinates cellular signaling after DNA double-strand breaks, oxidative stress, and cell-cycle checkpoint activation[1]. Mechanistically, ATM and ATR (ATM-Rad3-related) act as proximal DNA damage response kinases, but ATM is central to double-strand-break signaling, whereas ATR leads a parallel cascade activated by replication stress[2][3]. In disease contexts, ATM mutation causes ataxia-telangiectasia, a multisystem disorder involving neurodegeneration, immunodeficiency, radiosensitivity, cancer susceptibility, and genetic instability[4][5]. Compared with ATR, ATM deficiency creates experimental dependence on ATR in some cancer models, supporting ATR inhibition as a synthetic-lethal strategy in ATM-deficient prostate cancer and colorectal xenograft models[6][7]. For research applications, ATM inhibitors such as KU-55933 help interrogate ATM-dependent DNA damage signaling and have reduced HSV-1 replication and stromal keratitis severity in experimental corneal models[8].
References:
- [1]. Amirifar P, et al. Ataxia-telangiectasia: A review of clinical features and molecular pathology. Pediatr Allergy Immunol. 2019 May;30(3):277-288. [Content Brief]
- [2]. Mu JJ, et al. A proteomic analysis of ataxia telangiectasia-mutated (ATM)/ATM-Rad3-related (ATR) substrates identifies the ubiquitin-proteasome system as a regulator for DNA damage checkpoints. J Biol Chem. 2007 Jun 15;282(24):17330-4. [Content Brief]
- [3]. Balmus G, et al. Disease severity in a mouse model of ataxia telangiectasia is modulated by the DNA damage checkpoint gene Hus1. Hum Mol Genet. 2012 Aug 1;21(15):3408-20. [Content Brief]
- [4]. Meyn MS. Ataxia-telangiectasia, et al. Ataxia-telangiectasia, cancer and the pathobiology of the ATM gene. Clin Genet. 1999 May;55(5):289-304. [Content Brief]
- [5]. Putti S, et al. ATM Kinase Dead: From Ataxia Telangiectasia Syndrome to Cancer. Cancers (Basel). 2021 Nov 1;13(21):5498. [Content Brief]
- [6]. Gulliver C, et al. Ataxia-telangiectasia mutated and ataxia telangiectasia and Rad3-related kinases as therapeutic targets and stratification indicators for prostate cancer. Int J Biochem Cell Biol. 2022 Jun;147:106230. [Content Brief]
- [7]. Shao J, et al. Design, Synthesis, and Biological Evaluation of Potent and Selective Inhibitors of Ataxia Telangiectasia Mutated and Rad3-Related (ATR) Kinase for the Efficient Treatment of Cancer. Molecules. 2023 Jun 2;28(11):4521. [Content Brief]
- [8]. Alekseev O, et al. Inhibition of ataxia telangiectasia mutated (ATM) kinase suppresses herpes simplex virus type 1 (HSV-1) keratitis. Invest Ophthalmol Vis Sci. 2014 Feb 3;55(2):706-15. [Content Brief]
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ATR Related Products (41)
Related Products (41)
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Berzosertib
0 ImagesSynonyms: VE-822; VX-970; M6620Berzosertib (VE-822) is an orally active, CNS-penetrant, and selective ATR kinase inhibitor. Berzosertib blocks ATR kinase activity, abrogates G2/M cell cycle checkpoint, impairs DNA damage repair. Berzosertib induces apoptosis, inhibnits conlony migration, inhibits cell proliferation, and activates cGAS-STING axes in cancer cells. Berzosertib can be used for the research of cancers, such as head and neck squamous cell carcinoma, and colorectal cancer.
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Elimusertib
0 ImagesSynonyms: BAY 1895344
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Camonsertib
0 ImagesSynonyms: RP-3500; ATR inhibitor 4Camonsertib (RP-3500) is an orally active, selective ATR kinase inhibitor (ATRi) with an IC50 of 1.00 nM in biochemical assays. Camonsertib shows 30-fold selectivity for ATR over mTOR (IC50=120 nM) and >2,000-fold selectivity over ATM, DNA-PK, and PI3Kα kinases. Camonsertib has potent antitumor activity.
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Abd110
0 ImagesAbd110 is a selective ATR PROTAC degrader. Abd110 recruits Cereblon to induce the proteasomal degradation of ATR, and reduces the levels of phosphorylated ATR and downstream phosphorylated CHK1. Abd110 can be used for research on pancreatic cancer and cervical cancer.
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Gartisertib
0 ImagesSynonyms: VX-803; M4344; ATR inhibitor 2
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Elimusertib hydrochloride
0 ImagesCat. No.: HY-101566APurity: 99.85%Synonyms: BAY 1895344 hydrochloride
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Garcinone C
0 ImagesGarcinone C, a xanthone derivative, is a natural compound extracted from Garcinia oblongifolia that is used as an anti-inflammatory, astringency and granulation-promoting medicine, and has potential cytotoxic effects on certain cancers. Garcinone C stimulates the expression levels of ATR and 4E-BP1, arrests the cell cycle, inhibits cell viability of the human Nasopharyngeal carcinoma (NPC) cell lines CNE1, CNE2, HK1 and HONE1 in a time‑ and dose‑dependent manner through inhibition of Hedgehog signaling pathway. Garcinone C is orally active.
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AD1058
0 ImagesAD1058 is an orally active, selective, and BBB-permeable inhibitor of ATR (IC50: 1.6 nM). AD1058 exhibits anticancer activity by inhibiting tumor cell proliferation, inducing cell cycle arrest, and promoting apoptosis. AD1058 is suitable for research on advanced malignancies and brain metastases.
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PROTAC ATR degrader-1
0 ImagesPROTAC ATR degrader-1 is a ATR PROTAC degrader. PROTAC ATR degrader-1 promotes ubiquitination and degradation of ATR. PROTAC ATR degrader-1 facilitates the progression of cells through the G2/M phase, thereby impairing DNA repair and inducing Apoptosis. PROTAC ATR degrader-1 exerts anticancer effects against colorectal cancer either alone or in combination with Cisplatin (HY-17394). PROTAC ATR degrader-1 can be used in research related to colorectal cancer.
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PROTAC ATR degrader-2
0 ImagesPROTAC ATR degrader-2 is a selective ATR PROTAC degrader. PROTAC ATR degrader-2 degrades ATR in acute myeloid leukemia (AML) cells MV-4-11 and MOLM-13, with DC50 values of 22.9 nM and 34.5 nM, respectively. PROTAC ATR degrader-2 has an IC50 of 29.6 nM against ATR, and its IC50 values against ATM and PI3K are both greater than 2000 nM. PROTAC ATR degrader-2 induces apoptosis, DNA damage, and upregulates p53 expression. PROTAC ATR degrader-2 inhibits cancer cell proliferation through the kinase-independent function of ATR protein. PROTAC ATR degrader-2 is applicable to research related to acute myeloid leukemia.
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ATR-IN-14
0 ImagesCat. No.: HY-147566CAS No.: 2765785-88-2ATR-IN-14 (compound 1) is a potent ATR kinase inhibitor. ATR-IN-14 inhibits ATR signaling pathways downstream CHKI protein phosphorylation, with inhibition of 98.03% at 25 nM. ATR-IN-14 shows good anticancer activity in LoVo cells, with an IC50 of 64 nM.
