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Cai Y.,XING | Chai D.,XING | Pei F.,XING | Fang Y.,Peking University | And 8 more authors.
Journal of Pharmacy and Pharmacology | Year: 2012

Objectives To investigate the safety, pharmacokinetics and food effect of iptakalim in healthy adult Han Chinese volunteers. Methods Study 1 was a randomized open-label, Latin square designed, single-dose, three-period, self-control crossover study. Six men and six women received 5, 10 and 20 mg of iptakalim orally. Study 2 was a randomized, open-label, single-dose, two-period, self-control crossover study. Ten men were included and each subject received 5 mg iptakalim orally, fasting and nonfasting. Key findings No adverse effects were reported and no clinically meaningful changes in vital signs were found. Cmax, AUC 0-t and AUC 0-∞ were proportional over the dose levels of 5, 10 and 20 mg. Tmax, t1/2 and CL/F were similarly independent of dose level. In the 5 mg and 20 mg group, the Cmax, AUC 0-t and AUC 0-∞ in women were significantly higher than in men, although they showed no difference after correction by mg/kg doses in the 5 mg group. At the 5-mg dose level, no significant difference in pharmacokinetics was found in nonfasting and fasting subjects. Conclusions Single-dose pharmacokinetics of iptakalim showed dose proportionality over the dose levels of 5-20 mg. The pharmacokinetics showed gender differences in the 5 and 20 mg groups. Food had almost no impact on the pharmacokinetics at the 5 mg level. © 2011 Royal Pharmaceutical Society.

Chen M.,Center for Identification of Chinese Herbal Medicines | Chen M.,Tianjin Institute of Hygiene and Environmental Medicine | Qu X.,Center for Identification of Chinese Herbal Medicines | Zhang Z.,Tianjin Institute of Hygiene and Environmental Medicine | And 7 more authors.
Molecular Biology of the Cell | Year: 2016

We describe a novel functional interaction between ASK1 and PRMT5. We show that PRMT5 interacts with and methylates ASK1 at arginine residue 89 and thereby negatively regulates its activity by promoting the interaction between ASK1 and Akt and thus phosphorylating ASK1 at serine residue 83. Furthermore, the association between ASK1 and Akt is enhanced by VEGF stimulation, and PRMT5 is required for this association. Moreover, PRMT5-mediated ASK1 methylation impaired the H2O2-induced activity of ASK1, and this inhibitory effect of PRMT5 was abolished by replacement of arginine 89 with Trp or depletion of PRMT5 expression by RNA interference. Together the results demonstrate cross-talk between arginine methylation and serine phosphorylation in ASK1. © 2016 Billmann, Horn, et al.

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