Drug Safety on a Chip


The quality of decision-making in drug development is compromised by the limitations of currently available tools that cannot be applied early in the development process alongside bioactivity assays and have inadequate predictive power to weed out compounds that are likely to fail in late or clinical development phases. Solidus' technology enables high-throughput in vitro human toxicology studies to be performed at early stages of the drug development process.

MetaChip: Metabolizing Enzyme Toxicology Assay Chip

The Company's chip, in combination with the DataChip, for analyzing metabolism-generated toxicity. Proprietary technology for packaging human P450 enzymes into the MetaChip platform in a highly stable format, when matched against drug candidates simulates human metabolism by generating exact replicates of metabolites found in the body after drug administration. It enables early detection of hidden toxicity of metabolites during lead generation, lead optimization, and pre-clinical phases of drug development.

Cells are grown on individual micropillars of the DataChip then submersed in microwells of the complementary MetaChip.

DataChip: Data Analysis Toxicology Assay Chip

The Company's human cell screening chip has the capability to screen drug candidates for organ-specific toxicity at speeds commensurate with high-throughput bioactivity screening. Typical cell types accommodated for the DataChip are liver, kidney, bladder, skin, and neural, among others.

MesaChip: Metabolizing Enzyme Stability Assay Chip

The MesaChip is developed as an in vitro assay for P450 activity designed to improve drug development by evaluating the metabolism of large compound libraries earlier in the drug development process. The MesaChip incorporates human P450 isoforms in microwells on a chip and the reaction is monitored fluorescently by tracking consumption of NADPH and oxygen (consumed during the catalytic reaction). Simultaneous measurement of these molecules with time allows for the accurate determination of virtually any substrate's depletion rate without the use of a fluorescent or chromogenic substrate or costly LC-MS/MS analysis of product metabolites, two methods currently used to measure metabolic stability. This technology has already been demonstrated in a 384-well plate assay, the MesaPlate, and scale down of this technology to a MesaChip is under development.

Multizyme Chip: Multiple Enzyme Chip

The Multizyme Chip encompasses microarrays of enzymes on a chip to construct artificial synthetic pathways. Biosynthetically important enzymes are encapsulated into high-density microarray spots that have the capacity to perform large numbers of enzymatic reactions on a single chip, ultimately generating a large number of derivatives starting from a lead compound. Thus, the Multizyme Chip is specifically designed for high-throughput derivatization of lead compounds. It is well suited to transform complex lead compounds (e.g., natural products and multifunctional synthetics), as such molecules are difficult to modify selectively and controllably. In combination with the DataChip, it can be used for cell-based efficacy and toxicity screens for the rapid identification of biologically active derivatives. This approach represents a new paradigm for lead optimization by tapping into nature's vast biocatalytic repertoire. It is currently under development.

TeamChip: Transfected Enzyme and Metabolism Chip

The TeamChip encompasses microarrays of human cells expressing different combinations of metabolic enzymes on a chip. It is prepared by transfecting metabolic genes using a viral delivery system into immortalized human cells encapsulated in three-dimensional matrices arrayed on a micropillar chip. The TeamChip is being developed to mimic the first-pass metabolism of the human liver and to predict enzyme-specific hepatotoxicity, resulting from exposures to various chemicals, environmental pollutants, biologics, and therapeutic molecules or drugs. Thus, the reactivity of target compounds with individual human metabolic enzymes or combinations of enzymes in the human liver can be assessed and quantified at speeds commensurate with early-stage predictive human toxicity assessment. The TeamChip provides metabolic enzymes to virtually any human cell type, thereby providing predictions on xenobiotic toxicity in essentially any cell type in the body. By adjusting the expression levels of the various metabolic enzymes in human cells to match the enzyme levels representative of a subgroup or unique to an individual, the TeamChip chip can be tailored for analysis of drug compounds being developed for specific subgroups of the population and for individual patients. It is currently under development.