Validating novel DNA repair deficient cancer therapy targets and small molecule compounds
Validating novel DNA repair deficient cancer therapy targets and small molecule compounds
验证新型 DNA 修复缺陷癌症治疗靶点和小分子化合物
批准号：
10546636
负责人：
Richard Lipkin
金额：
$39.89万
依托单位：
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
项目状态：
已结题
起止时间：
2022-09-01 至 2024-08-31
关键词：
AgingAlkylationAromatic Polycyclic HydrocarbonsAutomobile DrivingBase Excision RepairsBindingBinding SitesBiological AssayCRISPR screenCancer PatientCandidate Disease GeneCatalytic DomainCell DeathCell LineChemicalsClustered Regularly Interspaced Short Palindromic RepeatsComputer softwareCytotoxic ChemotherapyD CellsDNA Double Strand BreakDNA RepairDNA Repair DisorderDNA Repair PathwayDNA Sequence AlterationDNA lesionDNA-Directed DNA PolymeraseDataDockingDouble Strand Break RepairDrug ScreeningERCC2 geneERCC6 geneExcision RepairFlow CytometryFutureGene MutationGenesGenetic TranscriptionGenomeGenomicsIndividualLesionLibrariesMalignant NeoplasmsMutationNonhomologous DNA End JoiningNucleotide Excision RepairPathway interactionsPatientsPharmaceutical PreparationsPhasePrecision therapeuticsRNARadiationSingle-Stranded DNASmall Business Innovation Research GrantSmall Business Technology Transfer ResearchSolid NeoplasmSomatic MutationStructure-Activity RelationshipTherapeuticToxic effectUracilbasebrca genecancer cellcancer therapycell typecytotoxicitygenome-widehomologous recombinationin silicoinhibitorinnovationlead optimizationmutantneoplastic cellnoveloxidationprecision medicinepreventrepairedscreeningsmall moleculesmall molecule inhibitorsmall molecule librariestargeted cancer therapytargeted treatmenttumortumorigenesisuracil-DNA glycosylase
中文摘要
翻译
摘要
单链DNA修复(SsDR)是防止基因组灾难的关键。AnaNeo Treeutics是
由DNA修复机制方面的专家创立。将我们团队之前的基础SSDR研究扩展到
分析>；61,000肿瘤的体细胞突变，产生等基因突变/野生型细胞系对，筛选
两对具有小分子文库的等基因细胞系，进行了计算和实验合成
致命性(SL)屏幕和使用最先进的薛定谔Maestro药物对接软件提名小
分子ssDR SL命中。在此第一阶段STTR项目中，我们建议验证候选目标和小型
分子抑制剂。总体而言，这项研究将提名创新的SSDR SL精确治疗靶点和小
在未来的第二阶段SBIR研究中，用于铅优化的分子命中。
英文摘要
Abstract
Single-strand DNA repair (ssDR) is critical for preventing genomic catastrophe. AnaNeo Therapeutics was
founded by experts in DNA repair mechanisms. Extending our team’s previous fundamental ssDR studies we
analyzed >61,000 tumors for somatic mutations, generated isogenic mutant/wild-type cell line pairs, screened
two isogenic cell line pairs with small molecule libraries, performed computational and experimental synthetic
lethality (SL) screens and used state-of-the-art Schrodinger Maestro drug docking software to nominate small
molecule ssDR SL hits. Here in this Phase I STTR project we propose to validate candidate targets and small
molecule inhibitors. Overall, this study will nominate innovative ssDR SL precision therapy targets and small
molecule hits for lead optimization in future Phase II SBIR studies.
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