A critical step in the drug discovery process, target validation involves demonstrating that a specific drug candidate modulates the intended target producing the desired therapeutic effect. Southern Research offers services in target validation that include evaluations in both in vitro systems and animal models. Our focused target validation studies can assist clients in determining whether a drug candidate hits its intended target. This vital information will help to optimize the drug discovery and development process and accelerate time to market.

Target Validation Capabilities

Southern Research has performed microarray expression analysis on 58 human tumor cell lines representative of 16 different tissues of origin, along with 42 matched tumor xenografts obtained from the same cell lines. Several cell lines adapted for drug resistance in vitro were also included.

When provided with a target of interest, we offer the capability to search our database of 58 cell lines and 42 tumor fragments in order to provide the relative expression levels of the target across these cell lines and xenograft models. These data can then be used to perform studies to validate that a specific drug candidate hits the intended target in vitro and in vivo. Additionally, Southern Research offers the capability to confirm the presence of the target protein by utilizing Western blot, immunohistochemistry, or flow cytometry, if desired.

Unsupervised hierarchical clustering was used to compare our cell line results with the cell-line analysis published by NCI in 2005, compare the genomic profiles of the xenograft model to that of the cell line from which it was derived, and learn whether xenograft and cell-line models from the same histotype exhibited similar genetic profiles. View these analyses (PDF format) .

Affymetrix whole genome microarray analysis of 42 human tumor xenograft models and the cell lines from which they were developed.

Based on the findings, Southern Research can help clients develop drug candidates in the following ways:

• We will search our genetic database for models that express your target of interest.
• Following in vitro screening of your compound, we will suggest other in vitro and/or in vivo models with similar genetic profile.
• Following in vivo screening, we will suggest other in vivo models with a similar genetic profile, often expanding the potential of your drug to be utilized in other histotypes.