title: Log-scale dose response of inhibitors on a chip.
abstract: We demonstrate the accommodation of log-scale concentration gradients of inhibitors on a single microfluidic chip with a semidirect dilution capability of reagents for the determination of the half-inhibitory concentration or IC(50). The chip provides a unique tool for hosting a wide-range of concentration gradient for studies that require an equal distribution of measuring points on a logarithmic scale. Using Matrix metalloproteinase IX and three of its inhibitors, marimastat, batimastat, and CP471474, we evaluated the IC(50) of each inhibitor with a single experiment. The present work could be applied to the systematic study of biochemical binding and inhibition processes particularly in the field of mechanistic enzymology and the pharmaceutical industry.
authors.affiliation: Materials Research and Education Center, Department of Mechanical Engineering, Auburn University, Auburn, Alabama 36849, United States.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Yun
authors.forename: Sachin
authors.initials: S
authors.lastname: Jambovane
authors.forename: Se-Kwon
authors.initials: SK
authors.lastname: Kim
authors.forename: Sung-Hak
authors.initials: SH
authors.lastname: Cho
authors.forename: Evert C
authors.initials: EC
authors.lastname: Duin
authors.forename: Jong Wook
authors.initials: JW
authors.lastname: Hong
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007700:Kinetics; D056656:Lab-On-A-Chip Devices; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D046208:Microchip Analytical Procedures / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; C100342:marimastat; D020780:Matrix Metalloproteinase 9