{"doi":"10.1101/2022.03.24.485659","title":"Target class profiling of small molecule methyltransferases","abstract":"Abstract Target class profiling (TCP) is a chemical biology approach to investigating 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 with clinical and biological importance. In this work we took a TCP approach to investigate inhibitory activity across a set of small molecule methyltransferases, 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 dataset we identified a novel inhibitor which selectively inhibits the small molecule methyltransferase HNMT, and demonstrated how this platform approach can be leveraged for a targeted drug discovery campaign using the example of HNMT.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303021,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9582,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":612764,"name":"Min Shen","orcid":"0000-0003-1912-126X","position":1,"is_corresponding":false},{"id":243295,"name":"Hui Guo","orcid":"0000-0002-1570-2545","position":2,"is_corresponding":false},{"id":995325,"name":"Ig-Jun Cho","orcid":null,"position":3,"is_corresponding":false},{"id":255126,"name":"Matthew D. Hall","orcid":"0000-0002-5073-442X","position":4,"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":"2026-07-19T00:32:20.348385Z","pmid":null,"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":[]}