DNA methyltransferase inhibitors: an updated patent review (2012-2015)
文献类型：期刊论文
| 作者 | Xu, Pan1,2; Hu, Guang1; Luo, Cheng2 ; Liang, Zhongjie1
|
| 刊名 | EXPERT OPINION ON THERAPEUTIC PATENTS
 |
| 出版日期 | 2016-09 |
| 卷号 | 26期号:9页码:1017-1030 |
| 关键词 | DNMT inhibitors (DNMTi) epigenetic therapy nucleotide derivatives drug combination allosteric inhibitor |
| ISSN号 | 1354-3776 |
| DOI | 10.1080/13543776.2016.1209488 |
| 文献子类 | Review |
| 英文摘要 | Introduction: DNA methyltransferases (DNMTs), important enzymes involved in epigenetic regulation of gene expression, represent promising targets in cancer therapy. DNMT inhibitors (DNMTi), which can modulate the aberrant DNA methylation pattern in a reversible way via inhibiting DNMT activity, have attracted significant attention in recent years. Areas covered: This review outlines the newly patented inhibitors targeting DNMTs, mainly incorporating small molecular inhibitors and oligonucleotide derivatives. The chemical structures, biological activity, and the encouraging clinical research in progress are delineated in detail. Expert opinion: Two drugs, azacitidine and decitabine, have evidently shown efficacy in hematologic malignancies, yet do not work well on solid tumors, have low specificity, substantial toxicity, and poor bioavailability. With the rapid advancement in systems biology, drug combinations, such as DNMTi, in conjugation with histone deacetylase inhibitors (HDACi) or immunotherapy, probably serve as an efficient way of implementing epigenetic therapy. Meanwhile, the resolved autoinhibitory structures of DNMTs afford a novel strategy for targeting the protein-protein interface involved in the autoinhi-bitory interactions. The molecular mechanism underlying the conformational transitions would also shed new light on the design of allosteric inhibitors. Both strategies would produce inhibitors with more selectivity compared to nucleotide derivatives. |
| WOS关键词 | ACUTE MYELOID-LEUKEMIA ; COVALENT HISTONE MODIFICATIONS ; TUMOR-SUPPRESSOR GENES ; PHASE-I ; METHYLATION INHIBITORS ; SEQUENTIAL AZACITIDINE ; PRIVILEGED STRUCTURES ; EPIGENETIC THERAPY ; NATURAL-PRODUCTS ; ELDERLY-PATIENTS |
| 资助项目 | National Basic Research Program[2015CB910304] ; National Natural Science Foundation of China[21472208] ; National Natural Science Foundation of China[81302700] ; Fund of State Key Laboratory of Toxicology and Medical Countermeasures, Academy of Military Medical Science[TMC201505] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000383294900005 |
| 出版者 | TAYLOR & FRANCIS LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275915]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Luo, Cheng; Liang, Zhongjie |
| 作者单位 | 1.Soochow Univ, Ctr Syst Biol, Suzhou 215006, Jiangsu, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Pan,Hu, Guang,Luo, Cheng,et al. DNA methyltransferase inhibitors: an updated patent review (2012-2015)[J]. EXPERT OPINION ON THERAPEUTIC PATENTS,2016,26(9):1017-1030. |
| APA | Xu, Pan,Hu, Guang,Luo, Cheng,&Liang, Zhongjie.(2016).DNA methyltransferase inhibitors: an updated patent review (2012-2015).EXPERT OPINION ON THERAPEUTIC PATENTS,26(9),1017-1030. |
| MLA | Xu, Pan,et al."DNA methyltransferase inhibitors: an updated patent review (2012-2015)".EXPERT OPINION ON THERAPEUTIC PATENTS 26.9(2016):1017-1030. |
入库方式： OAI收割
来源：上海药物研究所
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