验证新型 DNA 修复缺陷癌症治疗靶点和小分子化合物-猫眼课题宝

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：

ANANEO THERAPEUTICS INC.

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

来源：

https://reporter.nih.gov/project-details/10546636

关键词：

Aging Alkylation Aromatic Polycyclic Hydrocarbons Automobile Driving Base Excision Repairs Binding Binding Sites Biological Assay CRISPR screen Cancer Patient Candidate Disease Gene Catalytic Domain Cell Death Cell Line Chemicals Clustered Regularly Interspaced Short Palindromic Repeats Computer software Cytotoxic Chemotherapy D Cells DNA Double Strand Break DNA Repair DNA Repair Disorder DNA Repair Pathway DNA Sequence Alteration DNA lesion DNA-Directed DNA Polymerase Data Docking Double Strand Break Repair Drug Screening ERCC2 gene ERCC6 gene Excision Repair Flow Cytometry Future Gene Mutation Genes Genetic Transcription Genome Genomics Individual Lesion Libraries Malignant Neoplasms Mutation Nonhomologous DNA End Joining Nucleotide Excision Repair Pathway interactions Patients Pharmaceutical Preparations Phase Precision therapeutics RNA Radiation Single-Stranded DNA Small Business Innovation Research Grant Small Business Technology Transfer Research Solid Neoplasm Somatic Mutation Structure-Activity Relationship Therapeutic Toxic effect Uracil base brca gene cancer cell cancer therapy cell type cytotoxicity genome-wide homologous recombination in silico inhibitor innovation lead optimization mutant neoplastic cell novel oxidation precision medicine prevent repaired screening small molecule small molecule inhibitor small molecule libraries targeted cancer therapy targeted treatment tumor tumorigenesis uracil-DNA glycosylase

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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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海外基金

Validating novel DNA repair deficient cancer therapy targets and small molecule compounds

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