Small molecule targeting of chromatin writers in cancer
More than a decade after the launch of DNA methyltransferase and histone deacetylase inhibitors for the treatment of cancer, 2020 heralded the approval of the first histone methyltransferase inhibitor, revitalizing the concept that targeted manipulation of the chromatin regulatory landscape can have...
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| Veröffentlicht in: | Nature chemical biology 2022-02, Vol.18 (2), p.124-133 |
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| creator | Conery, Andrew R. Rocnik, Jennifer L. Trojer, Patrick |
| description | More than a decade after the launch of DNA methyltransferase and histone deacetylase inhibitors for the treatment of cancer, 2020 heralded the approval of the first histone methyltransferase inhibitor, revitalizing the concept that targeted manipulation of the chromatin regulatory landscape can have profound therapeutic impact. Three chromatin regulatory pathways—DNA methylation, histone acetylation and methylation—are frequently implicated in human cancer but hundreds of potentially druggable mechanisms complicate identification of key targets for therapeutic intervention. In addition to human genetics and functional screening, chemical biology approaches have proven critical for the discovery of key nodes in these pathways and in an ever-increasing complexity of molecularly defined human cancer contexts. This review introduces small molecule targeting approaches, showcases chemical probes and drug candidates for epigenetic writer enzymes, illustrates molecular features that may represent epigenetic dependencies and suggests translational strategies to maximize their impact in cancer therapy.
The Review summarized the recent progress in chemical probes and drug candidates for epigenetic writer enzymes and discussed the implication of targeting the chromatin regulatory landscape in cancer biology and therapy. |
| doi_str_mv | 10.1038/s41589-021-00920-5 |
| format | Article |
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| subjects | 631/92/458 631/92/613 692/699/67/1059 Acetylation Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Biochemical Engineering Biochemistry Biology Bioorganic Chemistry Cancer Cell Biology Chemistry Chemistry and Materials Science Chemistry/Food Science Chromatin Chromatin - metabolism Deoxyribonucleic acid DNA DNA methylation DNA methyltransferase DNA probes Drug Delivery Systems Drug development Enzymes Epigenetics Gene Expression Regulation, Neoplastic - drug effects Genetics Histone deacetylase Histone methyltransferase Histones Humans Neoplasms - genetics Neoplasms - metabolism Probes Review Article Writers |
| title | Small molecule targeting of chromatin writers in cancer |
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