On January 6, 2021 Pacylex Pharmaceuticals, an oncology company unlocking a new approach to cancer therapy, reported the publication in the journal Breast Cancer Research and Treatment data showing treatment with an N-myristoyltransferase (NMT) inhibitor reduces viability of cultured breast cancer cells and inhibits tumor growth in a mouse xenograft mouse model of human breast cancer (Press release, Pacylex Pharmaceuticals, JAN 6, 2021, View Source [SID1234645065]). Pacylex is developing this NMT inhibitor, PCLX-001, as a first in class therapy for various leukemias and lymphomas and also plans to study its effects on various solid tumors.

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"Despite the critical role myristoylation plays in cell survival, NMT1 and NMT2 protein levels have never been systematically studied in a large series of human cancers," said John Mackey, MD, Co-founder and Chief Medical Officer of Pacylex and first author on the paper. "Not only did we find a relationship between NMT2 levels and patient survival, but an NMT inhibitor was generally effective against breast cancer cell lines and inhibited human breast cancers grown in mice."

Dr. Mackey and colleagues studied the abundance and distribution of NMT1 and NMT2 proteins in normal breast tissue and a large cohort of primary breast adenocarcinomas from a prospective phase III clinical trial (n=706). NMT1 protein was observed in normal and most transformed breast epithelial tissue and was associated with better overall histologic grade, higher Ki67, and lower hormone expression. Though NMT2 protein was readily detected in normal breast epithelial tissue, it was undetectable in the majority of breast cancers. Detectable NMT2 protein correlated with significantly worse overall survival.

This extends the proof-of-concept for NMT inhibitors as potential cancer therapeutics for blood cancers, recently published in Nature Communications, to solid tumors as well, and supports the continued preparation for the first human clinical trial set to begin in early 2021. Both lymphoma and solid tumor patients including breast cancer will be enrolled in this initial study.

A link to the publication "N-myristoyltransferase proteins in breast cancer: prognostic relevance and validation as a new drug target" can be accessed here. The Alberta Cancer Foundation and the Cure Cancer Foundation both provided support for this research.

PCLX-001

PCLX-001 is a small molecule, first-in-class myristoylation inhibitor, originally developed by the University of Dundee Drug Discovery Unit as part of a program to treat African sleeping sickness funded by Wellcome Trust. Pacylex is developing PCLX-001, which has very good oral bioavailabilty, to treat cancers low in N-myristoyltransferase 2 (NMT2), a myristoylation enzyme whose deficiency is associated with higher mortality in leukemia and lymphoma. PCLX-001 selectively kills cancer cells and completely regresses (eliminates) tumors in animal models of acute myeloid leukemia (AML), diffuse large B-cell lymphoma (DLBCL) and Burkitt’s lymphoma (BL). PCLX-001 has also been shown to inhibit the growth of lung and breast cancer tumors in animal models. In tests using cultured cancer cells in vitro, PCLX-001 is at least ten times as potent as Ibrutinib (Imbruvica) and Dasatinib (Sprycel), two clinically approved drugs currently used to treat hematologic malignancies.