{"doi":"10.1021/acschembio.3c00124","title":"Target Class Profiling of Small-Molecule Methyltransferases","abstract":"Target class profiling (TCP) is a chemical biology approach to investigate understudied biological target classes. TCP is achieved by developing a generalizable assay platform and screening curated compound libraries to interrogate the chemical biological space of members of an enzyme family. In this work, we took a TCP approach to investigate inhibitory activity across a set of small-molecule methyltransferases (SMMTases), a subclass of methyltransferase enzymes, with the goal of creating a launchpad to explore this largely understudied target class. Using the representative enzymes nicotinamide N -methyltransferase (NNMT), phenylethanolamine N -methyltransferase (PNMT), histamine N -methyltransferase (HNMT), glycine N -methyltransferase (GNMT), catechol O -methyltransferase (COMT), and guanidinoacetate N -methyltransferase (GAMT), we optimized high-throughput screening (HTS)-amenable assays to screen 27,574 unique small molecules against all targets. From this data set, we identified a novel inhibitor which selectively inhibits the SMMTase HNMT and demonstrated how this platform approach can be leveraged for a targeted drug discovery campaign using the example of HNMT.","journal":"ACS Chemical Biology","year":2023,"id":354753,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1102276,"name":"Nate Hoxie","orcid":"0000-0001-5880-4165","position":1,"is_corresponding":false},{"id":239789,"name":"Min Shen","orcid":"0000-0002-8218-0433","position":2,"is_corresponding":false},{"id":243295,"name":"Hui Guo","orcid":"0000-0002-1570-2545","position":3,"is_corresponding":false},{"id":995325,"name":"Ig-Jun Cho","orcid":null,"position":4,"is_corresponding":false},{"id":1102768,"name":"Ipsita Chakraborty","orcid":null,"position":5,"is_corresponding":false},{"id":1102769,"name":"Brooklyn M. Aragon","orcid":null,"position":6,"is_corresponding":false},{"id":268294,"name":"Ganesha Rai","orcid":"0000-0001-9763-9641","position":7,"is_corresponding":false},{"id":353889,"name":"Samarjit Patnaik","orcid":"0000-0002-4265-7620","position":8,"is_corresponding":false},{"id":969854,"name":"John Janiszewski","orcid":null,"position":9,"is_corresponding":false},{"id":255126,"name":"Matthew D. Hall","orcid":"0000-0002-5073-442X","position":10,"is_corresponding":false},{"id":550314,"name":"Quinlin Hanson","orcid":"0000-0001-6033-8415","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T01:13:11.976628Z","pmid":"36976909","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}