ArticleMolecular pharmacology2015
The Novel Ribonucleotide Reductase Inhibitor COH29 Inhibits DNA Repair In Vitro.
Open access · bronzeAbstract read
In one paragraph
Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- RNA-mediated condensation of TFE3 oncofusions facilitates transcriptional hub formation to promote translocation renal cell carcinoma.Nature communications · 2025Article
- Blockade ofmBio · 2025Article
- Ribonucleotide reductase (RNR) inhibitors as target-based weapon for future cancer drug development.Future medicinal chemistry · 2025Review
- Clinical application and drug resistance mechanism of gemcitabine.Frontiers in cell and developmental biology · 2025Review
- Gallium Uncouples Iron Metabolism to Enhance Glioblastoma Radiosensitivity.International journal of molecular sciences · 2024Article
- Targeting of RRM2 suppresses DNA damage response and activates apoptosis in atypical teratoid rhabdoid tumor.Journal of experimental & clinical cancer research : CR · 2023Article
- Inhibitors of the Cancer Target Ribonucleotide Reductase, Past and Present.Biomolecules · 2022Review
- Article
- Radicals in Biology: Your Life Is in Their Hands.Journal of the American Chemical Society · 2021Article
- Novel Insights into the Molecular Regulation of Ribonucleotide Reductase in Adrenocortical Carcinoma Treatment.Cancers · 2021Article
- The changing investment in translational science by academic medical centers: HOPE in the Valley of Death.The Journal of clinical investigation · 2020Article
- Ribonucleotide Reductases: Structure, Chemistry, and Metabolism Suggest New Therapeutic Targets.Annual review of biochemistry · 2020Review
- Comprehensive analysis reveals a metabolic ten-gene signature in hepatocellular carcinoma.PeerJ · 2020Article
- A Novel Mechanism Driving Poor-Prognosis Prostate Cancer: Overexpression of the DNA Repair Gene, Ribonucleotide Reductase Small Subunit M2 (RRM2).Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Inhibition of CHK1 sensitizes Ewing sarcoma cells to the ribonucleotide reductase inhibitor gemcitabine.Oncotarget · 2017Article
- Stress-induced release of Oct-1 from the nuclear envelope is mediated by JNK phosphorylation of lamin B1.PloS one · 2017Article
- A Recurrent ERCC3 Truncating Mutation Confers Moderate Risk for Breast Cancer.Cancer discovery · 2016Article
- A Selective Small Molecule DNA2 Inhibitor for Sensitization of Human Cancer Cells to Chemotherapy.EBioMedicine · 2016Article
- Autophagy induction causes a synthetic lethal sensitization to ribonucleotide reductase inhibition in breast cancer cells.Oncotarget · 2016Article
- Deoxyribonucleotide metabolism, mutagenesis and cancer.Nature reviews. Cancer · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 2 countries.
Mei-Chuan ChenDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Bingsen ZhouDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Keqiang ZhangDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Yate-Ching YuanDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Frank UnDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Shuya HuDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Chih-Ming ChouDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Chun-Han ChenDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Jun WuDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Yan WangDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Xiyong LiuDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
D Lynne SmithDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Hongzhi LiDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Zheng LiuDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Charles D WardenDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Leila SuDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Linda H MalkasDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Young Min ChungDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Mickey C-T HuDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan.
Yun YenDepartments of Molecular Pharmacology (B.Z., K.Z., F.U., S.H., X.L., D.L.S., Y.Y.), Molecular Medicine (Y.-C.Y., H.L., Z.L., C.D.W., L.S.), Molecular and Cellular Biology (L.H.M.), and Division of Comparative Medicine (J.W., Y.W.), City of Hope National Medical Center, Duarte, California; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Stanford University School of Medicine, Stanford, California; (Y.M.C., M.C.-T.H.); Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy (M.-C.C.), and Graduate Institute of Pharmacognosy, College of Pharmacy, (M.-C.C), Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology (C.-H.C., Y.Y.), and Department of Biochemistry, School of Medicine, College of Medicine (C.-M.C.), Taipei Medical University, Taipei, Taiwan yyen@tmu.edu.tw.
Stanford University · USTaipei Medical University · TWCity Of Hope National Medical Center · USMolecular Oncology (United States) · US
Funding
Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3MDrug Development of Ribonucleotide Reductase InhibitorR01CA127541 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI HORNE, DAVID A. · 2008 to 2012
$1.7MThe Role of Regulation of FOXO3a in Tumor SuppressionR01CA113859 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HU, MICKEY C-T · 2006 to 2010
$1.2MNCI NIH HHS P30 CA033572NCI NIH HHS P30-CA033572NCI NIH HHS R01 CA113859NCI NIH HHS R01-CA113859NCI NIH HHS R01 CA127541NCI NIH HHS R01-CA127541
Abstract
COH29 [N-(4-(3,4-dihydroxyphenyl)-5-phenylthiazol-2-yl)-3,4-dihydroxybenzamide], a novel antimetabolite drug developed at City of Hope Cancer Center, has anticancer activity that stems primarily from the inhibition of human ribonucleotide reductase (RNR). This key enzyme in deoxyribonucleotide biosynthesis is the target of established clinical agents such as hydroxyurea and gemcitabine because of its critical role in DNA replication and repair. Herein we report that BRCA-1-defective human breast cancer cells are more sensitive than wild-type BRCA-1 counterparts to COH29 in vitro and in vivo. Microarray gene expression profiling showed that COH29 reduces the expression of DNA repair pathway genes, suggesting that COH29 interferes with these pathways. It is well established that BRCA1 plays a role in DNA damage repair, especially homologous recombination (HR) repair, to maintain genome integrity. In BRCA1-defective HCC1937 breast cancer cells, COH29 induced more double-strand breaks (DSBs) and DNA-damage response than in HCC1937 + BRCA1 cells. By EJ5- and DR-green fluorescent protein (GFP) reporter assay, we found that COH29 could inhibit nonhomologous end joining (NHEJ) efficiency and that no HR activity was detected in HCC1937 cells, suggesting that repression of the NHEJ repair pathway may be involved in COH29-induced DSBs in BRCA1-deficient HCC1937 cells. Furthermore, we observed an accumulation of nuclear Rad51 foci in COH29-treated HCC1937 + BRCA1 cells, suggesting that BRCA1 plays a crucial role in repairing and recovering drug-induced DNA damage by recruiting Rad51 to damage sites. In summary, we describe here additional biologic effects of the RNR inhibitor COH29 that potentially strengthen its use as an anticancer agent.
Indexed as
AnimalsAntimetabolites, AntineoplasticBenzamidesBRCA1 ProteinBreast NeoplasmsCell Line, TumorDNA Breaks, Double-StrandedDNA End-Joining RepairDNA RepairFemaleHeterograftsHumansMice, Inbred NODMutagenicity TestsNeoplasm TransplantationRibonucleotide ReductasesAntimetabolites, AntineoplasticBenzamidesBRCA1 ProteinN-(4-(3,4-dihydroxyphenyl)-5-phenylthiazol-2-yl)-3,4-dihydroxybenzamideRibonucleotide ReductasesThiazoles
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.