Novel and Highly Potent ATR Inhibitor M4344 Kills Cancer Cells With Replication Stress, and Enhances the Chemotherapeutic Activity of Widely Used DNA Damaging Agents.


Journal

Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535

Informations de publication

Date de publication:
08 2021
Historique:
received: 30 11 2020
revised: 26 01 2021
accepted: 25 05 2021
pubmed: 29 5 2021
medline: 19 2 2022
entrez: 28 5 2021
Statut: ppublish

Résumé

Although several ATR inhibitors are in development, there are unresolved questions regarding their differential potency, molecular signatures of patients with cancer for predicting activity, and most effective therapeutic combinations. Here, we elucidate how to improve ATR-based chemotherapy with the newly developed ATR inhibitor, M4344 using

Identifiants

pubmed: 34045232
pii: 1535-7163.MCT-20-1026
doi: 10.1158/1535-7163.MCT-20-1026
pmc: PMC9398135
doi:

Substances chimiques

BAY 1895344 0
Isoxazoles 0
Morpholines 0
Pyrazines 0
Pyrazoles 0
Deoxycytidine 0W860991D6
Irinotecan 7673326042
Topotecan 7M7YKX2N15
ATR protein, human EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins EC 2.7.11.1
berzosertib L423PRV3V3
Gemcitabine 0

Banques de données

ClinicalTrials.gov
['NCT02278250', 'NCT04149145']

Types de publication

Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1431-1441

Informations de copyright

©2021 The Authors; Published by the American Association for Cancer Research.

Références

Mol Cell. 2017 Jun 15;66(6):801-817
pubmed: 28622525
Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):
pubmed: 33536335
EMBO J. 1999 Mar 1;18(5):1397-406
pubmed: 10064605
Nat Rev Cancer. 2018 Sep;18(9):586-595
pubmed: 29899559
Nat Commun. 2019 Aug 9;10(1):3601
pubmed: 31399589
Mol Cell. 2015 Nov 19;60(4):547-60
pubmed: 26590714
Int J Cancer. 2021 Feb 1;148(3):769-779
pubmed: 32895958
iScience. 2018 Dec 21;10:247-264
pubmed: 30553813
Am J Cancer Res. 2015 Dec 15;6(1):97-104
pubmed: 27073727
J Clin Oncol. 2020 Sep 20;38(27):3195-3204
pubmed: 32568634
Sci Transl Med. 2020 Feb 19;12(531):
pubmed: 32075943
Nat Commun. 2016 Dec 13;7:13837
pubmed: 27958275
Cancer Res. 2019 Apr 15;79(8):1730-1739
pubmed: 30967400
Cell Rep. 2020 Oct 20;33(3):108296
pubmed: 33086069
Clin Cancer Res. 2018 Sep 1;24(17):4332-4345
pubmed: 29748182
BMC Cancer. 2014 Jul 04;14:483
pubmed: 24996846
Cancers (Basel). 2020 May 01;12(5):
pubmed: 32369904
Cancer Res. 2020 Sep 15;80(18):3841-3854
pubmed: 32690724
Eur J Cancer. 2019 Nov;121:7-18
pubmed: 31525487
Pharmacol Ther. 2020 Jun;210:107518
pubmed: 32109490
Oncogene. 2019 Apr;38(14):2451-2463
pubmed: 30532030
Clin Cancer Res. 2019 Nov 15;25(22):6581-6589
pubmed: 31227499
Oncotarget. 2016 Nov 22;7(47):76534-76550
pubmed: 27708213
Pharmacol Ther. 2020 Mar;207:107450
pubmed: 31836456
Cell. 2013 Nov 21;155(5):1088-103
pubmed: 24267891
Cancer Res. 2020 Aug 15;80(16):3305-3318
pubmed: 32522823
Transl Lung Cancer Res. 2018 Feb;7(1):32-49
pubmed: 29535911
Nat Rev Cancer. 2016 Jan;16(1):20-33
pubmed: 26678314
Nat Rev Mol Cell Biol. 2017 Oct;18(10):622-636
pubmed: 28811666
Nat Commun. 2018 Aug 17;9(1):3292
pubmed: 30120226
Nature. 2009 Oct 22;461(7267):1071-8
pubmed: 19847258
Br J Cancer. 2020 Oct;123(9):1424-1436
pubmed: 32741974
Sci Transl Med. 2016 Oct 26;8(362):362ps17
pubmed: 27797957
Nat Protoc. 2016 Feb;11(2):347-58
pubmed: 26797458
Trends Cancer. 2018 Nov;4(11):755-768
pubmed: 30352678
Clin Cancer Res. 2015 Nov 1;21(21):4780-5
pubmed: 26362996
J Clin Oncol. 2018 Jun 1;36(16):1594-1602
pubmed: 29252124
Pharmacol Ther. 2019 Sep;201:94-102
pubmed: 31128155
Sci Transl Med. 2016 Jul 6;8(346):346fs12
pubmed: 27384345
J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
pubmed: 10655437
Cancer Res. 2014 Dec 1;74(23):6968-79
pubmed: 25269479
Cell. 2017 Jul 27;170(3):564-576.e16
pubmed: 28753430
Cancer Cell. 2019 Jul 8;36(1):17-34.e7
pubmed: 31287989
Clin Transl Radiat Oncol. 2018 Jun 08;12:16-20
pubmed: 30073210
Mol Cancer Ther. 2020 Jan;19(1):26-38
pubmed: 31582533
Curr Biol. 2000 Apr 20;10(8):479-82
pubmed: 10801416

Auteurs

Ukhyun Jo (U)

Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, Bethesda, Maryland. ukhyun.jo@nih.gov pommier@nih.gov.

Ilya S Senatorov (IS)

Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.

Astrid Zimmermann (A)

Merck KGaA, Biopharma R&D, Translational Innovation Platform Oncology, Darmstadt, Germany.

Liton Kumar Saha (LK)

Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, Bethesda, Maryland.

Yasuhisa Murai (Y)

Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, Bethesda, Maryland.

Se Hyun Kim (SH)

Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, Bethesda, Maryland.
Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea.

Vinodh N Rajapakse (VN)

Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, Bethesda, Maryland.

Fathi Elloumi (F)

Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, Bethesda, Maryland.
General Dynamics Information Technology Inc., Fairfax, Virginia.

Nobuyuki Takahashi (N)

Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, Bethesda, Maryland.

Christopher W Schultz (CW)

Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, Bethesda, Maryland.

Anish Thomas (A)

Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, Bethesda, Maryland.

Frank T Zenke (FT)

Merck KGaA, Biopharma R&D, Translational Innovation Platform Oncology, Darmstadt, Germany.

Yves Pommier (Y)

Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, Bethesda, Maryland. ukhyun.jo@nih.gov pommier@nih.gov.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH