Multisubunit ion channels can adopt pharmacologically distinct forms depending on subunit stoichiometry, accessory factors or post-translational modifications. Production and screening of in vitro correlates that accurately reflected NaV1.7 as it exists in vivo addressed this biological complexity and resulted in compounds that blocked pain in vivo . We used Chromovert® technology to produce numerous cell lines comprising NaV1.7 alpha and beta subunits. Comparisons to alpha-only cell lines demonstrated that minimized target entities do not approximate the intact, multisubunit ion channel. Moreover, cross-comparative pharmacological characterization of numerous multisubunit cell lines enabled selection of a subset that were demonstrated as accurate in vitro correlates of NaV1.7 activity in vivo . At least 20 structurally distinct chemical series identified by parallel HTS of a high-diversity chemical compound library demonstrated efficacy in animal pain models, some with potencies greater than Gabapentin. Efficacious and potent clinical leads with desired selectivity and safety for other complex targets may be developed by coupling previously existing drug development infrastructure and expertise with the new speed and scale with which it is now possible to implement physiologically relevant panels of cell based assays. Results for ENaC and panels of CFTR mutants, additional multisubunit targets and panels that had been out of reach in their intact and native forms, will also be presented.