{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:16:43Z","timestamp":1784809003457,"version":"3.55.0"},"reference-count":6,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T00:00:00Z","timestamp":1647129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000001","name":"Alberta Cancer Foundation","doi-asserted-by":"publisher","award":["27369"],"award-info":[{"award-number":["27369"]}],"id":[{"id":"10.13039\/501100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Cure Cancer Foundation","award":["\u2018World\u2019s Longest Hockey Game\u2019 and \u2018World\u2019s Longest Baseball Game\u2019"],"award-info":[{"award-number":["\u2018World\u2019s Longest Hockey Game\u2019 and \u2018World\u2019s Longest Baseball Game\u2019"]}]},{"name":"Pacylex Pharmaceuticals Inc.","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have limited treatment options, particularly if they are transplantation or chimeric antigen receptor (CAR) T-cell ineligible, and novel therapeutics are needed. An 86-year-old woman with relapsed DLBCL received a novel, first-in-class small molecule inhibitor of N-myristoyltransferase (NMT) as the initial patient on a phase I dose escalation trial. Daily oral administration of 20 mg PCLX-001 tablets produced a pharmacokinetic profile suitable for single daily dosing: rapid oral absorption, followed by an apparent elimination half-life of 16 h, without systemic accumulation of drug by day 15. Pharmacodynamic tests showed no clear change in NMT1 and NMT2 levels or selected NMT substrate Lyn and HGAL protein levels in normal circulating blood mononuclear cells, suggesting a higher dose will be required for normal tissue toxicity. The patient did not experience any dose-limiting toxicities but had disease progression after 28 days of study therapy. Dose escalation continues in other patients in this first-in-human study of a new class of anticancer drug. We conclude that PCLX-001 oral monotherapy has suitable pharmacokinetic parameters for dose escalation, and that higher doses are required to achieve pharmacodynamic evidence of on-target activity in normal tissues. The current protocol is appropriately designed to achieve these ends, and the study proceeds without modification.<\/jats:p>","DOI":"10.3390\/curroncol29030158","type":"journal-article","created":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T22:29:43Z","timestamp":1647210583000},"page":"1939-1946","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Novel, First-in-Human, Oral PCLX-001 Treatment in a Patient with Relapsed Diffuse Large B-Cell Lymphoma"],"prefix":"10.3390","volume":"29","author":[{"given":"Randeep","family":"Sangha","sequence":"first","affiliation":[{"name":"Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7050-1471","authenticated-orcid":false,"given":"Neal M.","family":"Davies","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G2H1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshin","family":"Namdar","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Spratlin","sequence":"additional","affiliation":[{"name":"Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwan","family":"Beauchamp","sequence":"additional","affiliation":[{"name":"Pacylex Pharmaceuticals Inc., Edmonton, AB T5J4P6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc G.","family":"Berthiaume","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2H7, Canada"},{"name":"Pacylex Pharmaceuticals Inc., Edmonton, AB T5J4P6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Mackey","sequence":"additional","affiliation":[{"name":"Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G1Z2, Canada"},{"name":"Pacylex Pharmaceuticals Inc., Edmonton, AB T5J4P6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/s41589-018-0077-5","article-title":"Structural and genomic decoding of human and plant myristoylomes reveals a definitive recognition pattern","volume":"14","author":"Castrec","year":"2018","journal-title":"Nat. Chem. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.plipres.2006.05.002","article-title":"Potential role of N-myristoyltransferase in cancer","volume":"46","author":"Selvakumar","year":"2007","journal-title":"Prog. Lipid Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5348","DOI":"10.1038\/s41467-020-18998-1","article-title":"Targeting N-myristoylation for therapy of B-cell lymphomas","volume":"11","author":"Beauchamp","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s10549-020-06037-y","article-title":"N-myristoyltransferase proteins in breast cancer: Prognostic relevance and validation as a new drug target","volume":"186","author":"Mackey","year":"2021","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3362","DOI":"10.1182\/blood-2019-124934","article-title":"Initial Characterization and Toxicology of an Nmt Inhibitor in Development for Hematologic Malignancies","volume":"134","author":"Weickert","year":"2019","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1182\/blood-2021-153613","article-title":"An Open-Label, First-in-Human, Phase I Trial of Daily Pclx-001","volume":"138","author":"Sangha","year":"2021","journal-title":"Blood"}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/29\/3\/158\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:35:51Z","timestamp":1760135751000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/29\/3\/158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,13]]},"references-count":6,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["curroncol29030158"],"URL":"https:\/\/doi.org\/10.3390\/curroncol29030158","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,13]]}}}