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 (39)
Related Products (39)
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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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ICT10336
0 ImagesCat. No.: HY-161838ICT10336 is a hypoxia-responsive prodrug of ATR inhibitor, AZD6738 (HY-19323). ICT10336 is hypoxia-activated and specifically releases AZD6738 only in hypoxic conditions in vitro. This can inhibit ATR activation (T1989 and S428 phosphorylation) and subsequently abrogate HIF1a-mediated adaptation of hypoxic cancers cells, thus selectively inducing cell death in 2D and 3D cancer models. ICT10336 is a metabolic substrate of CYPOR activity.
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ATR ligand 2
0 ImagesCat. No.: HY-182017CAS No.: 3060178-60-8ATR ligand 2 (Compound 26) is a ATR PROTAC ligand. ATR ligand 2 can be conjugated with E3 ligase Ligand (HY-W077589A) and linker to synthesize PROTAC ATR degrader-3 (HY-182016).
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ATR-IN-10
0 ImagesCat. No.: HY-144214CAS No.: 2713577-93-4ATR-IN-10 is a potent and highly selective inhibitor of ataxia telangiectasia mutated and Rad3-Related (ATR) kinase with an IC50 value of 2.978 μM.
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ATR-IN-19
0 ImagesCat. No.: HY-147190CAS No.: 2648989-61-9ATR-IN-19 (Compound 15 R-configure) is an ATR inhibitor.
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ATR-IN-21
0 ImagesCat. No.: HY-153393CAS No.: 2905312-17-4ATR-IN-21 (compound 60) is a potent ATR inhibitor with an IC50 value of <1000 nM.
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ATR-IN-17
0 ImagesCat. No.: HY-147569CAS No.: 2761194-15-2ATR-IN-17 (compound 88) is a potent ATR kinase inhibitor. ATR-IN-17 shows good anticancer activity in LoVo cells, with an IC50 of 1 nM.
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Abd141
0 ImagesCat. No.: HY-187195Abd141 is a dual PROTAC degrader of ATR and Aurora kinase A (AURKA), with DC50 values of 97.7 nM and 6.7 nM, respectively. Abd141 inhibits the proliferation of acute lymphoblastic leukemia cells. Abd141 can be used in the research of acute lymphoblastic leukemia.
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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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PROTAC ATR degrader-3
0 ImagesCat. No.: HY-182016CAS No.: 3126270-11-6PROTAC ATR degrader-3 is a potent CRBN-based ATR PROTAC degrader with a DC50 of 127 nM. PROTAC ATR degrader-3 also degrades CHK1 with an DC50 of 135 nM. PROTAC ATR degrader-3 inhibits cancer cells proliferation, migration and invasion, triggers apoptosis and induces S phase arrest and DNA damage. PROTAC ATR degrader-3 achieves tumor growth inhibition in LoVo xenograft mouse model without apparent toxicity. PROTAC ATR degrader-3 can be used for the research of colorectal cancer.
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ATR-IN-29
0 ImagesCat. No.: HY-153729CAS No.: 2761193-67-1ATR-IN-29 is a potent and orally active ATR kinase inhibitor with an IC50 value of 1 nM. ATR-IN-29 shows antiproliferative activity.
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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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ATR-IN-18
0 ImagesCat. No.: HY-147570CAS No.: 2766407-55-8ATR-IN-18 (compound 2) is an orally active and potent ATR kinase inhibitor, with an IC50 of 0.69 nM. ATR-IN-18 shows antiproliferative activity in LoVo cells, with an IC50 of 37.34 nM. ATR-IN-18 has anti-tumor activity.
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ATR-IN-16
0 ImagesCat. No.: HY-147568CAS No.: 2756589-62-3ATR-IN-16 (compound 46) is a potent ATR kinase inhibitor. ATR-IN-16 shows good anticancer activity in LoVo cells, with an IC50 of 410 nM.
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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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