Preclinical pharmacokinetics of the radiomitigator KZ-41 in rats

@article{Zeng2011PreclinicalPO,
  title={Preclinical pharmacokinetics of the radiomitigator KZ-41 in rats},
  author={Kui Zeng and Karin Emmons Thompson and Chaela Sickbert Presley and Duane D. Miller and Charles R. Yates},
  journal={Xenobiotica},
  year={2011},
  volume={41},
  pages={1006 - 1012}
}
KZ-41, a quinic acid derivative, significantly reduces mortality in a murine model of hematopoietic acute radiation syndrome. The purpose of this study was to evaluate the systemic pharmacokinetics, elimination, and oral bioavailability of KZ-41 in rats. Male Sprague-Dawley rats (n = 6 per group) received a single dose (10 mg/kg) of KZ-41 administered either intravenously via the jugular vein or orally via gavage. In vitro stability was determined using both rat liver microsomes and the… Expand
Metabolism schemes of chlorogenic, quinic and caffeic acid derivatives in rats deduced by molecular fragments detected with optimized UPLC–APCI-MS/MS conditions
Abstract The synthesized chlorogenic, quinic, and caffeic acid derivatives with antifungal activity were investigated on their metabolism and biotransformation properties in rats detected byExpand
Novel quinic acid derivative KZ-41 prevents retinal endothelial cell apoptosis without inhibiting retinoblastoma cell death through p38 signaling.
TLDR
KZ-41 protects REC against melphalan-induced upregulation of ICAM-1 and apoptosis through p38 MAPK-dependent pathways, and appears to be the primary pathway involved in melphAlan-induced REC apoptosis. Expand
Small molecule FGF23 inhibitors increase serum phosphate and improve skeletal abnormalities in Hyp mice
TLDR
Testing in a pre-clinical Hyp mouse homologue of XLH a direct connect analogue (8n) that exhibited the greatest stability in microsomal assays, and 13a that exhibited increased in vitro potency found that pharmacological inhibition of FGF23 with either of these compounds blocked FGF 23 signaling and significantly increased serum phosphate and 1,25(OH)2D concentrations in Hyp mice. Expand
The quinic acid derivative KZ-41 prevents glucose-induced caspase-3 activation in retinal endothelial cells through an IGF-1 receptor dependent mechanism
TLDR
It is demonstrated that KZ-41 blocks caspase-3 activation by triggering phosphorylation of the PI3K regulatory subunit and its downstream target Akt, suggesting that QA derivatives may offer therapeutic benefit in ischemic retinopathies. Expand
Translational Novel Quinic Acid Derivative KZ-41 Prevents Retinal Endothelial Cell Apoptosis Without Inhibiting Retinoblastoma Cell Death Through p 38 Signaling
Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TennesseeExpand

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