Development and Evolution of DNA-Dependent Protein Kinase Inhibitors toward Cancer Therapy

DNA-PK Inhibitor Peposertib Amplifies Radiation-Induced Inflammatory Micronucleation and Enhances TGFβ/PD-L1 Targeted Cancer Immunotherapy

(2022) Michael I. Carr et al.   MOLECULAR CANCER RESEARCH

The DNA-PK inhibitor AZD7648 sensitizes patient derived ovarian cancer xenografts to pegylated liposomal doxorubicin and olaparib preventing abdominal metastases

(2022) Alessia Anastasia et al.   MOLECULAR CANCER THERAPEUTICS

Structural insights into inhibitor regulation of the DNA repair protein DNA-PKcs

(2022) Shikang Liang et al.   NATURE

DNA-PK promotes activation of the survival kinase AKT in response to DNA damage through an mTORC2-ECT2 pathway

(2022) Liu Liu et al.   Science Signaling

Pre-clinical activity of the oral DNA-PK inhibitor, peposertib (M3814), combined with radiation in xenograft models of cervical cancer

(2022) Sushmita B. Gordhandas et al.   Scientific Reports

Inhibition of DNA-PK may improve response to neoadjuvant chemoradiotherapy in rectal cancer

(2022) Mary Smithson et al.   NEOPLASIA

Structure of an activated DNA-PK and its implications for NHEJ

(2021) Xuemin Chen et al.   MOLECULAR CELL

Phosphoinositide 3-Kinase (PI3K) Reactive Oxygen Species (ROS)-Activated Prodrug in Combination with Anthracycline Impairs PI3K Signaling, Increases DNA Damage Response and Reduces Breast Cancer Cell Growth

(2021) Rosalin Mishra et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

A phase 1b study of the Notch inhibitor crenigacestat (LY3039478) in combination with other anticancer target agents (taladegib, LY3023414, or abemaciclib) in patients with advanced or metastatic solid tumors

(2021) Analia Azaro et al.   INVESTIGATIONAL NEW DRUGS

Phase 1 cohort expansion study of LY3023414, a dual PI3K/mTOR inhibitor, in patients with advanced mesothelioma

(2021) Marjorie G. Zauderer et al.   INVESTIGATIONAL NEW DRUGS

Inhibition of DNA-PK with AZD7648 sensitizes tumor cells to radiotherapy and induces type I interferon-dependent durable tumor control

(2021) Kyoko Nakamura et al.   CLINICAL CANCER RESEARCH

Mol* Viewer: modern web app for 3D visualization and analysis of large biomolecular structures

(2021) David Sehnal et al.   NUCLEIC ACIDS RESEARCH

Molecular mechanisms involved in DNA repair in human cancers: An overview of PI3k/Akt signaling and PIKKs crosstalk

(2021) Forough Alemi et al.   JOURNAL OF CELLULAR PHYSIOLOGY

DNA‐PKc inhibition overcomes taxane resistance by promoting taxane‐induced DNA damage in prostate cancer cells

(2021) Olivia S. Chao et al.   PROSTATE

DNA-PK inhibitor peposertib enhances p53-dependent cytotoxicity of DNA double-strand break inducing therapy in acute leukemia

(2021) Eric Haines et al.   Scientific Reports

HPV16 E6 enhances the radiosensitivity in HPV-positive human head and neck squamous cell carcinoma by regulating the miR-27a-3p/SMG1 axis

(2021) Dan Long et al.   Infectious Agents and Cancer

DNA-Dependent Protein Kinase Catalytic Subunit: The Sensor for DNA Double-Strand Breaks Structurally and Functionally Related to Ataxia Telangiectasia Mutated

(2021) Yoshihisa Matsumoto et al.   Genes

DNA-PK inhibition by M3814 enhances chemosensitivity in non-small cell lung cancer

(2021) Manni Wang et al.   Acta Pharmaceutica Sinica B

Activation of homologous recombination in G1 preserves centromeric integrity

(2021) Duygu Yilmaz et al.   NATURE

Radiosensitisation of SCCVII tumours and normal tissues in mice by the DNA-dependent protein kinase inhibitor AZD7648

(2021) Cho R. Hong et al.   RADIOTHERAPY AND ONCOLOGY

DNA-PK Inhibitor, M3814, as a New Combination Partner of Mylotarg in the Treatment of Acute Myeloid Leukemia

(2020) Michael I. Carr et al.   Frontiers in Oncology

Pharmacologic Inhibitor of DNA-PK, M3814, Potentiates Radiotherapy and Regresses Human Tumors in Mouse Models

(2020) Frank T. Zenke et al.   MOLECULAR CANCER THERAPEUTICS

Radiosensitising Cancer Using Phosphatidylinositol-3-Kinase (PI3K), Protein Kinase B (AKT) or Mammalian Target of Rapamycin (mTOR) Inhibitors

(2020) Kasun Wanigasooriya et al.   Cancers

M3814, a DNA-PK Inhibitor, Modulates ABCG2-Mediated Multidrug Resistance in Lung Cancer Cells

(2020) Zhuo-Xun Wu et al.   Frontiers in Oncology

Targeting the PI3K pathway and DNA damage response as a therapeutic strategy in ovarian cancer

(2020) Tzu-Ting Huang et al.   CANCER TREATMENT REVIEWS

Phase 1 dose-escalation study of a novel oral PI3K/mTOR dual inhibitor, LY3023414, in patients with cancer

(2020) Shunsuke Kondo et al.   INVESTIGATIONAL NEW DRUGS

DNMT1 Enhances the Radiosensitivity of HPV-Positive Head and Neck Squamous Cell Carcinomas via Downregulating SMG1

(2020) Chunlin Zhang et al.   OncoTargets and Therapy

The molecular basis and disease relevance of non-homologous DNA end joining

(2020) Bailin Zhao et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

A first-in-man phase 1 study of the DNA-dependent protein kinase inhibitor peposertib (formerly M3814) in patients with advanced solid tumours

(2020) Mark T. J. van Bussel et al.   BRITISH JOURNAL OF CANCER

Dual mTOR/DNA-PK Inhibitor CC-115 Induces Cell Death in Melanoma Cells and Has Radiosensitizing Potential

(2020) Felix Bürkel et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Therapeutic implications of p53 status on cancer cell fate following exposure to ionizing radiation and the DNA-PK inhibitor M3814

(2019) Qing Sun et al.   MOLECULAR CANCER RESEARCH

Hypoxia-selective radiosensitisation by SN38023, a bioreductive prodrug of DNA-dependent protein kinase inhibitor IC87361

(2019) Way Wua Wong et al.   BIOCHEMICAL PHARMACOLOGY

Oxidative Cyclization‐Induced Activation of a Phosphoinositide 3‐Kinase Inhibitor for Enhanced Selectivity of Cancer Chemotherapeutics

(2019) Haizhou Zhu et al.   ChemMedChem

Selective DNA-PKcs inhibition extends the therapeutic index of localized radiotherapy and chemotherapy

(2019) Catherine E. Willoughby et al.   JOURNAL OF CLINICAL INVESTIGATION

AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity

(2019) Jacqueline H. L. Fok et al.   Nature Communications

Phase 2 study of LY3023414 in patients with advanced endometrial cancer harboring activating mutations in the PI3K pathway

(2019) Maria M. Rubinstein et al.   CANCER

The Discovery of 7-Methyl-2-[(7-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino]-9-(tetrahydro-2H-pyran-4-yl)-7,9-dihydro-8H-purin-8-one (AZD7648), a Potent and Selective DNA-Dependent Protein Kinase (DNA-PK) Inhibitor

(2019) Frederick W. Goldberg et al.   JOURNAL OF MEDICINAL CHEMISTRY

Vanillin derivative VND3207 activates DNA-PKcs conferring protection against radiation-induced intestinal epithelial cells injury in vitro and in vivo

(2019) Ming Li et al.   TOXICOLOGY AND APPLIED PHARMACOLOGY

Activity of M3814, an Oral DNA-PK Inhibitor, In Combination with Topoisomerase II Inhibitors in Ovarian Cancer Models

(2019) Hannah C. Wise et al.   Scientific Reports

First-In-Human Phase I Study Of A Dual mTOR Kinase And DNA-PK Inhibitor (CC-115) In Advanced Malignancy

(2019) Pamela Munster et al.   Cancer Management and Research

A First-in-Human Phase 1 Study of LY3023414, an Oral PI3K/mTOR Dual Inhibitor, in Patients with Advanced Cancer

(2018) Johanna C. Bendell et al.   CLINICAL CANCER RESEARCH

Ataxia–telangiectasia gene (ATM) mutation heterozygosity in breast cancer: a narrative review

(2018) K.J. Jerzak et al.   Current Oncology

The DNA-PK Inhibitor VX-984 Enhances the Radiosensitivity of Glioblastoma Cells GrownIn Vitroand as Orthotopic Xenografts

(2018) Cindy R. Timme et al.   MOLECULAR CANCER THERAPEUTICS

Inhibition of DNA‑PK activity sensitizes A549 cells to X‑ray irradiation by inducing the ATM‑dependent DNA damage response

(2018) Lina Yang et al.   Molecular Medicine Reports

VX-984 is a selective inhibitor of non-homologous end joining, with possible preferential activity in transformed cells

(2018) Atif J. Khan et al.   Oncotarget

Akt1 Stimulates Homologous Recombination Repair of DNA Double-Strand Breaks in a Rad51-Dependent Manner

(2017) Katharina Mueck et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor‐Naïve Advanced Pancreatic Neuroendocrine Tumors

(2017) Ramon Salazar et al.   ONCOLOGIST

Identification of DNA-PKcs as a primary resistance factor of TIC10 in hepatocellular carcinoma cells

(2017) Long Cheng et al.   Oncotarget

CC-115, a dual inhibitor of mTOR Kinase and DNA-PK, blocks DNA damage repair pathways and selectively inhibits ATM-deficient cell growth in vitro

(2017) Toshiya Tsuji et al.   Oncotarget

Activating Akt1 mutations alter DNA double strand break repair and radiosensitivity

(2017) S. Oeck et al.   Scientific Reports

Phase II study of dual phosphoinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235 in patients with locally advanced or metastatic transitional cell carcinoma

(2016) Emmanuel Seront et al.   BJU INTERNATIONAL

Dual TORK/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia

(2016) R. Thijssen et al.   BLOOD

Health risks for ataxia-telangiectasia mutated heterozygotes: a systematic review, meta-analysis and evidence-based guideline

(2016) N.J.H. van Os et al.   CLINICAL GENETICS

Synthesis, structure elucidation, DNA-PK and PI3K and anti-cancer activity of 8- and 6-aryl-substituted-1-3-benzoxazines

(2016) Rick Morrison et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Characterization of LY3023414, a Novel PI3K/mTOR Dual Inhibitor Eliciting Transient Target Modulation to Impede Tumor Growth

(2016) M. C. Smith et al.   MOLECULAR CANCER THERAPEUTICS

Targeting hyperactivated DNA-PKcs by KU0060648 inhibits glioma progression and enhances temozolomide therapy via suppression of AKT signaling

(2016) Tian Lan et al.   Oncotarget

Identification of DNA-PKcs as a primary resistance factor of salinomycin in osteosarcoma cells

(2016) Yun-fang Zhen et al.   Oncotarget

KU-0060648 inhibits hepatocellular carcinoma cells through DNA-PKcs-dependent and DNA-PKcs-independent mechanisms

(2016) Min-Bin Chen et al.   Oncotarget

Dual Phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor is an effective radiosensitizer for colorectal cancer

(2015) Yu-Hsuan Chen et al.   CANCER LETTERS

XLS (c9orf142) is a new component of mammalian DNA double-stranded break repair

(2015) A Craxton et al.   CELL DEATH AND DIFFERENTIATION

Optimization of a Series of Triazole Containing Mammalian Target of Rapamycin (mTOR) Kinase Inhibitors and the Discovery of CC-115

(2015) Deborah S. Mortensen et al.   JOURNAL OF MEDICINAL CHEMISTRY

PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair

(2015) T. Ochi et al.   SCIENCE

Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway

(2015) Mengtan Xing et al.   Nature Communications

NSCLC cells demonstrate differential mode of cell death in response to the combined treatment of radiation and a DNA-PKcs inhibitor

(2015) Lan Yu et al.   Oncotarget

The Dual PI3K/mTOR Inhibitor NVP-BEZ235 Is a Potent Inhibitor of ATM- and DNA-PKCs-Mediated DNA Damage Responses

(2015) Bipasha Mukherjee et al.   NEOPLASIA

SMG-1 suppresses CDK2 and tumor growth by regulating both the p53 and Cdc25A signaling pathways

(2013) Evgenia Gubanova et al.   CELL CYCLE

Inhibition of DNA Double-Strand Break Repair by the Dual PI3K/mTOR Inhibitor NVP-BEZ235 as a Strategy for Radiosensitization of Glioblastoma

(2013) Carlos Rodrigo Gil del Alcazar et al.   CLINICAL CANCER RESEARCH

1-Substituted (Dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-ones Endowed with Dual DNA-PK/PI3-K Inhibitory Activity

(2013) Céline Cano et al.   JOURNAL OF MEDICINAL CHEMISTRY

Enhanced cytotoxicity of PARP inhibition in mantle cell lymphoma harbouring mutations in both ATM and p53

(2012) Chris T. Williamson et al.   EMBO Molecular Medicine

Chemosensitization of Cancer Cells by KU-0060648, a Dual Inhibitor of DNA-PK and PI-3K

(2012) J. M. Munck et al.   MOLECULAR CANCER THERAPEUTICS

The RNA surveillance protein SMG1 activates p53 in response to DNA double-strand breaks but not exogenously oxidized mRNA

(2011) Jennifer S. Gewandter et al.   CELL CYCLE

A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations

(2011) Luis I Toledo et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells

(2011) A. G. Patel et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

XLF Regulates Filament Architecture of the XRCC4·Ligase IV Complex

(2010) Michal Hammel et al.   STRUCTURE

Effect of ZSTK474, a Novel Phosphatidylinositol 3-Kinase Inhibitor, on DNA-Dependent Protein Kinase

(2009) Dexin Kong et al.   BIOLOGICAL & PHARMACEUTICAL BULLETIN

Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion

(2009) S. E. Golding et al.   MOLECULAR CANCER THERAPEUTICS

The pyridinylfuranopyrimidine inhibitor, PI-103, chemosensitizes glioblastoma cells for apoptosis by inhibiting DNA repair

(2009) M -A Westhoff et al.   ONCOGENE

Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity

(2008) S.-M. Maira et al.   MOLECULAR CANCER THERAPEUTICS

PKBα/Akt1 Acts Downstream of DNA-PK in the DNA Double-Strand Break Response and Promotes Survival

(2008) Lana Bozulic et al.   MOLECULAR CELL

Radioprotection of 4-hydroxy-3,5-dimethoxybenzaldehyde (VND3207) in culture cells is associated with minimizing DNA damage and activating Akt

(2007) Hong Zheng et al.   EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES