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Half-maximal Inhibitory Concentration (half-maximal + inhibitory_concentration)
Selected AbstractsBlockade of HERG K+ channel by an antihistamine drug brompheniramine requires the channel binding within the S6 residue Y652 and F656JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2008Sang-Joon Park Abstract A number of clinically used drugs block delayed rectifier K+ channels and prolong the duration of cardiac action potentials associated with long QT syndrome. This study investigated the molecular mechanisms of voltage-dependent inhibition of human ether- a-go-go -related gene (HERG) delayed rectifier K+ channels expressed in HEK-293 cells by brompheniramine, an antihistamine. Brompheniramine inhibited HERG current in a concentration-dependent manner with the half-maximal inhibitory concentration (IC50) value of 1.7 µm at 0 mV. A block of HERG current by brompheniramine was enhanced by progressive membrane depolarization and showed significantly negative shift in voltage-dependence of channel activation. Inhibition of HERG current by brompheniramine showed time-dependence. The S6 residue HERG mutant Y652A and F656C largely reduced the blocking potency of HERG current. These results indicate that brompheniramine mainly inhibited the HERG potassium channel through the residue Y652 and F656 and these residues may be an obligatory determinant in inhibition of HERG current for brompheniramine. Copyright © 2007 John Wiley & Sons, Ltd. [source] Synergistic effect of oligochitosan and silicon on inhibition of Monilinia fructicola infectionsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 4 2010Lingyu Yang Abstract BACKGROUND: Oligochitosan has broad-spectrum antimicrobial activity and shows an obvious inhibitory effect on phytopathogens. In addition, as an exogenous elicitor, it can induce various defence responses, including affecting the activities of several defence-related enzymes and substances in some plants. Owing to this dual function of oligochitosan, it can be used to control postharvest diseases of fruits. Silicon, like oligochitosan, also has a dual function. In this study the synergistic effect of oligochitosan and silicon on the decay control of apple fruit was investigated. RESULTS:In vitro, both oligochitosan and silicon significantly inhibited spore germination, germ tube elongation and mycelial growth of Monilinia fructicola, with higher concentrations having a greater effect. The synergistic effect of oligochitosan and silicon at half-maximal inhibitory concentration on disease control at 25 °C was much better than the effect of oligochitosan or silicon alone, not only in vitro but also in vivo. CONCLUSION: The results showed that a combination of oligochitosan and silicon had a synergistic effect on the control of disease caused by M. fructicola in apple fruit at 25 °C. Copyright © 2010 Society of Chemical Industry [source] High-quality crystals of human haematopoietic prostaglandin D synthase with novel inhibitorsACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 7 2010Sachiko Takahashi Human haematopoietic prostaglandin D synthase (H-PGDS; EC 5.3.99.2) produces prostaglandin D2, an allergic and inflammatory mediator, in mast cells and Th2 cells. H-PGDS has been crystallized with novel inhibitors with half-maximal inhibitory concentrations (IC50) in the low nanomolar range by the counter-diffusion method onboard the Russian Service Module on the International Space Station. The X-ray diffraction of a microgravity-grown crystal of H-PGDS complexed with an inhibitor with an IC50 value of 50,nM extended to 1.1,Å resolution at 100,K using SPring-8 synchrotron radiation, which is one of the highest resolutions obtained to date for this protein. [source] Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapyBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2009Kunihiro Suzuki WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Co-administration of proton pump inhibitors (PPIs) increases plasma methotrexate (MTX) concentration in cancer patients receiving high-dose MTX (HDMTX) therapy. , There is controversy as to whether or not co-administration of PPIs affects plasma MTX elimination in HDMTX therapy. , Inhibitory activity of PPIs on breast cancer resistance protein (BCRP) is a possible mechanism for the drug interaction between MTX and PPIs. WHAT THIS STUDY ADDS , Co-administration of a PPI (omeprazole, lansoprazole, or rabeprazole) was more frequently observed in the delayed MTX elimination group than in the normal MTX elimination group. , Multiple logistic regression analysis with adjustment for significant covariates revealed that PPI co-administration was a significant risk factor for delayed plasma MTX elimination. , The half-maximal inhibitory concentration of each PPI in inhibiting BCRP function was much higher than the therapeutic unbound concentration in the plasma. AIM To assess whether or not co-administration of proton pump inhibitors (PPIs) is a risk factor for delayed elimination of plasma methotrexate (MTX) in high-dose MTX (HDMTX) therapy for malignant diseases. METHODS To assess the effects of PPI co-administration on elimination of plasma MTX, we examined plasma MTX concentration data on 171 cycles of HDMTX therapy performed in 74 patients. We performed multiple logistic regression analysis to evaluate PPI co-administration as a risk factor. Inhibitory potencies of omeprazole, lansoprazole, rabeprazole and pantoprazole on MTX transport via breast cancer resistance protein (BCRP, ABCG2) were also investigated in an in vitro study using membrane vesicles expressing human BCRP. RESULTS We identified co-administration of PPIs as a risk factor for delayed elimination (odds ratio 2.65, 95% confidence interval 1.03, 6.82) as well as renal and liver dysfunction. All four PPIs inhibited BCRP-mediated transport of MTX, with half-maximal inhibitory concentrations of 5.5,17.6 µM , considerably higher than the unbound plasma concentrations of the PPIs. CONCLUSIONS Our results support previous findings suggesting that PPI co-administration is associated with delayed elimination of plasma MTX in patients with HDMTX therapy. This drug interaction, however, cannot be explained solely by the inhibitory effects of PPIs on BCRP-mediated MTX transport. [source] | ||||||||||