title: Finding chemical drugs for genetic diseases.
abstract: Chemical drugs provide alternative treatments for genetic diseases in addition to gene therapy. Inherited diseases arising from gain-of-function (GOF) or loss-of-function (LOF) mutations of certain genes can be ameliorated by the antagonists and/or agonists of the target genes. However, a premise for this chemical therapeutic strategy is that the GOF/LOF mutations in drug targets have a negligible influence on drug-target binding. Here, we analyze the disease-causing mutations [derived from Online Mendelian Inheritance in Man (OMIM)] in successful drug targets. We found that >70% of the mutations are located far from the drug-binding sites (>12 Å), and most of the other mutations are unlikely to have adverse effects on drug binding, supporting the chemical strategy for combating genetic diseases.
authors.affiliation: National Key Laboratory of Crop Genetic Improvement, Agricultural Bioinformatics Key Laboratory of Hubei Province, College of Informatics, Huazhong Agricultural University, Wuhan 430070, PR China; Institute of Functional Nano & Soft Materials (FUNSOM) and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu 215123, PR China.
authors.forename: Hui-Yong
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM) and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu 215123, PR China; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, PR China. Electronic address: tingjunhou@zju.edu.cn.
authors.forename: Ting-Jun
authors.initials: TJ
authors.lastname: Hou
authors.affiliation: National Key Laboratory of Crop Genetic Improvement, Agricultural Bioinformatics Key Laboratory of Hubei Province, College of Informatics, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address: zhy630@mail.hzau.edu.cn.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Zhang
mesh_terms: D030342:Genetic Diseases, Inborn / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D009154:Mutation