Zelenirstat, also known as PCLX-001, is an investigational new drug that is being evaluated for the treatment of cancer and as an antiviral agent. It is a small molecule inhibitor targets both N-myristoyltransferase 1 (NMT1) and N-myristoyltransferase 2 (NMT2) proteins, which are responsible for myristoylation. Its dual mechanism of action disrupts both cell signaling and energy production in cancer cells.
Zelenirstat is a strong pan-N myristoyl transferase inhibitor, which prevents addition of myristic acid into penultimate glycine of protein with myristoylation signal, and initially has been introduced as anti-tumor drug.[1][2][3] It has completed phase I clinical trial and is going through escalation phase.[4] Its prototype DDD85646 and its analogue IMP-1088 have strong antiviral activities against viruses that required myristoylated proteins to complete their life cycle, including hemorrhagic viruses, such as lassa and argentinian virus, and pox viruses, such as vaccinia and monkeypox.[5][6]
Mechanism of action
Zelenirstat acts by inhibiting NMT I and II enzymes, which are required to complete the myristoylation of proteins. Without myristoylation, these proteins are targeted for proteasomal degradation.[7]
^Sangha RS, Jamal R, Spratlin J, Kuruvilla J, Sehn LH, Weickert M, et al. (June 2024). "Final results of a first-in-human phase I dose escalation trial of daily oral zelenirstat, a n-myristoyltransferase inhibitor, in patients with advanced solid tumors and relapsed/refractory B-cell lymphomas". Journal of Clinical Oncology. 42 (16_suppl): 3082. doi:10.1200/JCO.2024.42.16_suppl.3082. ISSN0732-183X.
