{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["10(6)"],"submitter":["Kawai J"],"pubmed_abstract":["Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) plays a key role in one-carbon (1C) metabolism in human mitochondria, and its high expression correlates with poor survival of patients with various types of cancer. An isozyme-selective MTHFD2 inhibitor is highly attractive for potential use in cancer treatment. Herein, we disclose a novel isozyme-selective MTHFD2 inhibitor DS44960156, with a tricyclic coumarin scaffold, which was initially discovered via high-throughput screening (HTS) and improved using structure-based drug design (SBDD). DS44960156 would offer a good starting point for further optimization based on the following features: (1) unprecedented selectivity (>18-fold) for MTHFD2 over MTHFD1, (2) a molecular weight of less than 400, and (3) good ligand efficiency (LE)."],"journal":["ACS medicinal chemistry letters"],"pagination":["893-898"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6580548"],"repository":["biostudies-literature"],"pubmed_title":["Structure-Based Design and Synthesis of an Isozyme-Selective MTHFD2 Inhibitor with a Tricyclic Coumarin Scaffold."],"pmcid":["PMC6580548"],"pubmed_authors":["Suzuki M","Ohki H","Ota M","Kawai J","Shimada T","Toki T","Inoue H","Matsui S","Sugihara C","Takaishi S","Matsui Y","Nakayama K","Matsuhashi N"],"additional_accession":[]},"is_claimable":false,"name":"Structure-Based Design and Synthesis of an Isozyme-Selective MTHFD2 Inhibitor with a Tricyclic Coumarin Scaffold.","description":"Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) plays a key role in one-carbon (1C) metabolism in human mitochondria, and its high expression correlates with poor survival of patients with various types of cancer. An isozyme-selective MTHFD2 inhibitor is highly attractive for potential use in cancer treatment. Herein, we disclose a novel isozyme-selective MTHFD2 inhibitor DS44960156, with a tricyclic coumarin scaffold, which was initially discovered via high-throughput screening (HTS) and improved using structure-based drug design (SBDD). DS44960156 would offer a good starting point for further optimization based on the following features: (1) unprecedented selectivity (>18-fold) for MTHFD2 over MTHFD1, (2) a molecular weight of less than 400, and (3) good ligand efficiency (LE).","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jun","modification":"2026-05-01T18:20:03.585Z","creation":"2020-06-17T07:02:35Z"},"accession":"S-EPMC6580548","cross_references":{"pubmed":["31223444"],"doi":["10.1021/acsmedchemlett.9b00069"]}}