U-74389G

Lazaroid U-74389G (LAZ) is a 21-aminosteroid that has radioprotective effects against radiation-induced lipid peroxidation. Researchers utilized a liposomal formulation to evaluate LAZ radioprotective and antiproliferative effects in a glioblastoma mouse model. LAZ liposomal formulations reduced tumor growth by 65%. LAZ also protected brain tissue from radiation-induced lipid peroxidation by reducing MDA concentration by 50%¹.

Novel antioxidant compounds, the pyrrolopyrimidines, has been discovered, possess increased efficacy & potency in protecting cultured neurons against iron-induced lipid peroxidative injury and as much as a 5-fold increase in brain uptake compared with U-74006G. They appear to quench lipid peroxidation reactions by electron-donating and/or radical-trapping mechanisms².

Increased levels of oxidative damage to DNA, lipids and proteins have been detected by a range of assays in post-mortem tissues from patients with Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis, and at least some of these changes may occur early in disease progression.

U-74006F appears to localize in the blood-brain barrier. Studies have demonstrated that lymphocyte-derived microparticles (LMPs) impair endothelial cell function. The antioxidant U-74389G were partially protective against the antiproliferative effects of LMPs³.

1. Effects of lazaroid U-74389G liposomes in a glioblastoma mouse model. J Clin Oncol (Meeting Abstracts) Fady Ibrahim et al, May 2012 vol. 30 no. 15_suppl 2098.
2. Pyrrolopyrimidines: Novel Brain-Penetrating Antioxidants with Neuroprotective Activity in Brain Injury and Ischemia Models. E. D. HALL, et al., JPET 281:895–904, 1997,
3. Lymphocytic microparticles inhibit angiogenesis by stimulating oxidative stress and negatively regulating VEGF-induced pathways. Chun Yang, et al, Am J Physiol Regul Integr Comp Physiol 294: R467–R476, 2008.