2017
2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity
Sulkowski PL, Corso CD, Robinson ND, Scanlon SE, Purshouse KR, Bai H, Liu Y, Sundaram RK, Hegan DC, Fons NR, Breuer GA, Song Y, Mishra-Gorur K, De Feyter HM, de Graaf RA, Surovtseva YV, Kachman M, Halene S, Günel M, Glazer PM, Bindra RS. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Science Translational Medicine 2017, 9 PMID: 28148839, PMCID: PMC5435119, DOI: 10.1126/scitranslmed.aal2463.Peer-Reviewed Original ResearchConceptsIsocitrate dehydrogenase 1PARP inhibitor sensitivityPossible therapeutic strategiesHomologous recombination defectsTherapeutic strategiesTumor xenograftsInhibitor sensitivityPathologic processesSmall molecule inhibitorsIDH1/2 mutationsTumor progressionIDH2 mutationsMutant IDHPolymerase inhibitorsGlioma cellsTumor cellsHR deficiencyPARP inhibitionIDH mutationsInhibitory effectDehydrogenase 1Neomorphic activityMutant IDH1 enzymeDependent dioxygenasesMutant cells
2016
Characterization of Cardiac Glycoside Natural Products as Potent Inhibitors of DNA Double-Strand Break Repair by a Whole-Cell Double Immunofluorescence Assay
Surovtseva YV, Jairam V, Salem AF, Sundaram RK, Bindra RS, Herzon SB. Characterization of Cardiac Glycoside Natural Products as Potent Inhibitors of DNA Double-Strand Break Repair by a Whole-Cell Double Immunofluorescence Assay. Journal Of The American Chemical Society 2016, 138: 3844-3855. PMID: 26927829, PMCID: PMC5530877, DOI: 10.1021/jacs.6b00162.Peer-Reviewed Original ResearchConceptsRing finger protein 8DNA double-strand break repairDouble-strand break repairSmall molecule inhibitorsDSB repairBreak repairDNA damage checkpoint protein 1DNA damage response networkNatural productsSmall moleculesP53-binding protein 1Sites of DSBsFinger protein 8Protein 1Glycoside natural productsDNA repair pathwaysNew small molecule inhibitorsClass of compoundsBinding protein 1Small molecule DNALarge compound librariesPotent inhibitorRepair pathwaysCardiac glycosidesSecondary assays