{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["3(3)"],"submitter":["Eriksen-Gjerstad M"],"pubmed_abstract":["Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma that remains incurable with the treatment options available today. In the present study, we have identified the dihydroorotate dehydrogenase (DHODH), an essential enzyme for the <i>de novo </i>biosynthesis of pyrimidine-based nucleotides, to be overexpressed in MCL in comparison to healthy peripheral blood mononuclear cells (PBMC). In vitro inhibition of the DHODH activity using a newly developed DHODH inhibitor, namely (<i>R</i>)-HZ05, can induce MCL cell death in the nanomolar range independently than the P53 status of the investigated cell lines. Moreover, the combination of (<i>R</i>)-HZ05 with tyrosine kinase inhibitor shows the synergistic activity on cell death. Pre-clinical investigation on the efficacy of (<i>R</i>)-HZ05 shows t"],"journal":["EJHaem"],"pagination":["913-918"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9422018"],"repository":["biostudies-literature"],"pubmed_title":["Dihydroorotate dehydrogenase inhibition acts synergistically with tyrosine kinase inhibitors to induce apoptosis of mantle cell lymphoma cells."],"pmcid":["PMC9422018"],"pubmed_authors":["Gelebart P","Tveit Karlsen I","Locke F","Mc Cormack E","Baran-Marszak F","Pastor-Fernandez A","Eriksen-Gjerstad M","Ladds M","Fandalyuk Z","Papp B","Benjaminsen S"],"additional_accession":[]},"is_claimable":false,"name":"Dihydroorotate dehydrogenase inhibition acts synergistically with tyrosine kinase inhibitors to induce apoptosis of mantle cell lymphoma cells.","description":"Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma that remains incurable with the treatment options available today. In the present study, we have identified the dihydroorotate dehydrogenase (DHODH), an essential enzyme for the <i>de novo </i>biosynthesis of pyrimidine-based nucleotides, to be overexpressed in MCL in comparison to healthy peripheral blood mononuclear cells (PBMC). In vitro inhibition of the DHODH activity using a newly developed DHODH inhibitor, namely (<i>R</i>)-HZ05, can induce MCL cell death in the nanomolar range independently than the P53 status of the investigated cell lines. Moreover, the combination of (<i>R</i>)-HZ05 with tyrosine kinase inhibitor shows the synergistic activity on cell death. Pre-clinical investigation on the efficacy of (<i>R</i>)-HZ05 shows t","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Aug","modification":"2025-04-05T12:10:50.937Z","creation":"2025-04-05T12:10:50.937Z"},"accession":"S-EPMC9422018","cross_references":{"pubmed":["36051066"],"doi":["10.1002/jha2.434"]}}