Interpreting Steep Dose-Response Curves in Early Inhibitor Discovery Export

@article{citeulike:3758192, abstract = {doi: 10.1021/jm061103g Many screening hits inhibit enzymes with steep dose-response curves, which are considered pathological. Three models might explain these curves: multisite binding, an inhibitor phase transition, or stoichiometric inhibition caused by a high enzyme to Kd ratio. Experiments with promiscuous aggregators, for which steep curves are common, suggest that these curves owe to stoichiometric inhibition, which predicts that IC50 should vary linearly with enzyme concentration. Most steep dose-response curves in screening may be due to this effect.}, author = {Shoichet, Brian K.}, citeulike-article-id = {3758192}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/jm061103g}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/jm061103g}, comment = {Alex F. 12/10/08}, day = {1}, doi = {10.1021/jm061103g}, journal = {Journal of Medicinal Chemistry}, keywords = {cpjc, enzymes}, month = {December}, number = {25}, pages = {7274--7277}, posted-at = {2008-12-09 00:05:24}, priority = {0}, title = {Interpreting Steep Dose-Response Curves in Early Inhibitor Discovery}, url = {http://dx.doi.org/10.1021/jm061103g}, volume = {49}, year = {2006} }

TY - JOUR ID - citeulike:3758192 L3 - citeulike-article-id:3758192 N2 - doi: 10.1021/jm061103g Many screening hits inhibit enzymes with steep dose-response curves, which are considered pathological. Three models might explain these curves: multisite binding, an inhibitor phase transition, or stoichiometric inhibition caused by a high enzyme to Kd ratio. Experiments with promiscuous aggregators, for which steep curves are common, suggest that these curves owe to stoichiometric inhibition, which predicts that IC50 should vary linearly with enzyme concentration. Most steep dose-response curves in screening may be due to this effect. IS - 25 JF - Journal of Medicinal Chemistry EP - 7277 TI - Interpreting Steep Dose-Response Curves in Early Inhibitor Discovery VL - 49 SP - 7274 KW - cpjc KW - enzymes N1 - Alex F. 12/10/08 AU - Shoichet, Brian PY - 2006/12/01/ UR - http://dx.doi.org/10.1021/jm061103g ER -