BXQ-350 nanovesicle formulation [Saposin C-DOPS]: ...Saposin C + Lipid/Ceramide = “Nano Cell” A stable, nanovesicle formulation composed of a synthetic form of the human glycoprotein saposin C (SapC) linked to the phospholipid dioleoylphosphatidylserine (DOPS), with potential antineoplastic activity. Upon intravenous administration, the BXQ-350 nanovesicle formulation selectively targets and preferentially accumulates in tumor vessels and cells, due to the leaky nature of tumor vasculature and the presence of phosphatidylserine (PS) lipids in tumor cell membranes. Upon binding to the phospholipids in the tumor cell membrane, SapC fuses with the membrane and is internalized leading to its accumulation within the internal membrane. SapC becomes active in the acidic tumor microenvironment and as a lysosomal sphingolipid activator protein, activates lysosomal enzymes, such as beta-glucosidase, acid sphingomyelinase, and beta-galactosylceramidase. This leads to the degradation of glucosylceramide and sphingomyelin, and the conversion of galactosylceramide to ceramide, respectively. This elevates intracellular ceramide levels, activates caspases and induces ceramide-mediated apoptosis, which together lead to an inhibition of tumor cell growth. SapC plays key roles in lipid transport and organization of biological membranes and has strong lipid membrane binding activity. https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=785725 Bexion's BXQ-350 MOA:
May 2016 Competing interests Xiaoyang Qi, Ph.D. is listed as an inventor on the patent for the technology (SapC-DOPS) that is the subject of this research. Consistent with current Cincinnati Children’s Hospital Medical Center policies, the development and commercialization of this technology has been licensed to Bexion Pharmaceuticals, LLC, in which Dr. Qi holds a minor (<5 %) equity interest. This work was supported in part by R01CA158372-01A0 (to X. Qi), R21NS095047-01A0 (to X. Qi), Brain Tumor Center Research Funds and Hematology-Oncology Programmatic Support from University of Cincinnati College of Medicine (to X. Qi), and New Drug State Key Project Grant Number 009ZX09102-205 (to X. Qi). https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-016-0519-1
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