Preclinical pharmacokinetics of the radiomitigator KZ-41 in rats

  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},
  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.
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
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
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


Treatment of chemotherapy-induced leukopenia in a rat model with aqueous extract from Uncaria tomentosa.
  • Y. Sheng, R. Pero, H. Wagner
  • Biology, Medicine
  • Phytomedicine : international journal of phytotherapy and phytopharmacology
  • 2000
Data showing enhanced effects on DNA repair and immune cell proliferative response support a general immune enhancement and the recovery by C-Med-100 treatment was a more natural process than Neupogen because all fractions of white blood cells were proportionally increased while Ne upogen mainly elevated the neutrophil cells. Expand
Enhanced DNA repair, immune function and reduced toxicity of C-MED-100, a novel aqueous extract from Uncaria tomentosa.
Female W/Fu rats were gavaged daily with a water-soluble extract of Uncaria tomentosa supplied commercially by CampaMed at the doses of 0, 5, 10, 20, 40 and 80 mg/kg for 8 consecutive weeks and no acute or chronic toxicity signs were observed symptomatically. Expand
Metabolite Profiling of Hydroxycinnamate Derivatives in Plasma and Urine after the Ingestion of Coffee by Humans: Identification of Biomarkers of Coffee Consumption
Urinary dihydrocaffeic acid-3-O-sulfate and feruloylglycine are potentially very sensitive biomarkers for the consumption of relatively small amounts of coffee, indicating absorption in the large intestine and the probable involvement of catabolism by colonic bacteria. Expand
Chlorogenic acid is absorbed in its intact form in the stomach of rats.
For the first time, chlorogenic acid is quickly absorbed in the rat stomach in its intact form and its metabolites could be detected by HPLC-electrospray ionization-MS-MS. Expand
Species differences in the aromatization of quinic acid in vivo and the role of gut bacteria.
The results support the view that quinic acid and shikimic acid are aromatized by the gut flora in man and the Old World monkeys. Expand
Synthesis and biological evaluation of quinic acid derivatives as anti-inflammatory agents.
A novel series of non-toxic QA amides that potently inhibit NF-kappaB, despite their lack of anti-oxidant activity are discovered. Expand
Absorption and metabolism of caffeic acid and chlorogenic acid in the small intestine of rats.
The present results show that chlorogenic acid is absorbed and hydrolysed in the small intestine, in contrast to numerous flavonoids, which appears to be governed largely by their uptake into the gut mucosa. Expand
C-Med 100, a hot water extract of Uncaria tomentosa, prolongs lymphocyte survival in vivo.
Accumulation is concluded that accumulation is most likely due to prolonged cell survival, because adoptive transfer experiments demonstrated that C-Med 100 treatment significantly prolonged lymphocyte survival in peripheral lymphoid organs, without increasing their proliferation rate. Expand
Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS.
Practical, experimental approaches for studying, identifying, and eliminating the effect of matrix on the results of quantitative analyses by HPLC-MS/MS are described and it is demonstrated that, for the investigational drug under study, the matrix effect was clearly observed when ISP interface was utilized but it was absent when the HN interface was employed. Expand
Quinic acid aromatization in the rat. Urinary hippuric acid and catechol excretion following the singular or repeated administration of quinic acid.
  • S. Indahl, R. Scheline
  • Chemistry, Medicine
  • Xenobiotica; the fate of foreign compounds in biological systems
  • 1973
Incubation of quinic acid with rat caecal microorganisms resulted in the formation of benzoic acid under aerobic and anaerobic conditions and small amounts of protocatechuic acid were detected when aerobic conditions were employed. Expand