Quinazolinone derivatives as inhibitors of homologous recombinase RAD51. 2017

Ambber Ward, and Lilong Dong, and Jonathan M Harris, and Kum Kum Khanna, and Fares Al-Ejeh, and David P Fairlie, and Adrian P Wiegmans, and Ligong Liu
Personalised Medicine, QIMR Berghofer Medical Research Institute, Herston Rd, Herston, Brisbane, Queensland, Australia.

RAD51 is a vital component of the homologous recombination DNA repair pathway and is overexpressed in drug-resistant cancers, including aggressive triple negative breast cancer (TNBC). A proposed strategy for improving therapeutic outcomes for patients is through small molecule inhibition of RAD51, thereby sensitizing tumor cells to DNA damaging irradiation and/or chemotherapy. Here we report structure-activity relationships for a library of quinazolinone derivatives. A novel RAD51 inhibitor (17) displays up to 15-fold enhanced inhibition of cell growth in a panel of TNBC cell lines compared to compound B02, and approximately 2-fold increased inhibition of irradiation-induced RAD51 foci formation. Additionally, compound 17 significantly inhibits TNBC cell sensitivity to DNA damage, implying a potentially targeted therapy for cancer treatment.

UI MeSH Term Description Entries
D011799 Quinazolines A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring. Quinazoline
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002934 Cinnamates Derivatives of cinnamic acid (the structural formula: phenyl-HC Cinnamate
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining

Related Publications

Ambber Ward, and Lilong Dong, and Jonathan M Harris, and Kum Kum Khanna, and Fares Al-Ejeh, and David P Fairlie, and Adrian P Wiegmans, and Ligong Liu
April 2012, Journal of medicinal chemistry,
Ambber Ward, and Lilong Dong, and Jonathan M Harris, and Kum Kum Khanna, and Fares Al-Ejeh, and David P Fairlie, and Adrian P Wiegmans, and Ligong Liu
February 2012, Journal of receptor and signal transduction research,
Ambber Ward, and Lilong Dong, and Jonathan M Harris, and Kum Kum Khanna, and Fares Al-Ejeh, and David P Fairlie, and Adrian P Wiegmans, and Ligong Liu
December 2006, The Journal of biological chemistry,
Ambber Ward, and Lilong Dong, and Jonathan M Harris, and Kum Kum Khanna, and Fares Al-Ejeh, and David P Fairlie, and Adrian P Wiegmans, and Ligong Liu
December 2004, The Journal of biological chemistry,
Ambber Ward, and Lilong Dong, and Jonathan M Harris, and Kum Kum Khanna, and Fares Al-Ejeh, and David P Fairlie, and Adrian P Wiegmans, and Ligong Liu
November 2007, Molecular cell,
Ambber Ward, and Lilong Dong, and Jonathan M Harris, and Kum Kum Khanna, and Fares Al-Ejeh, and David P Fairlie, and Adrian P Wiegmans, and Ligong Liu
August 2019, European journal of medicinal chemistry,
Ambber Ward, and Lilong Dong, and Jonathan M Harris, and Kum Kum Khanna, and Fares Al-Ejeh, and David P Fairlie, and Adrian P Wiegmans, and Ligong Liu
January 2017, Frontiers in microbiology,
Ambber Ward, and Lilong Dong, and Jonathan M Harris, and Kum Kum Khanna, and Fares Al-Ejeh, and David P Fairlie, and Adrian P Wiegmans, and Ligong Liu
June 2011, ACS chemical biology,
Ambber Ward, and Lilong Dong, and Jonathan M Harris, and Kum Kum Khanna, and Fares Al-Ejeh, and David P Fairlie, and Adrian P Wiegmans, and Ligong Liu
January 2023, Viruses,
Ambber Ward, and Lilong Dong, and Jonathan M Harris, and Kum Kum Khanna, and Fares Al-Ejeh, and David P Fairlie, and Adrian P Wiegmans, and Ligong Liu
January 2022, Chemical & pharmaceutical bulletin,
Copied contents to your clipboard!