Optimization of the drug discovery process using agarose resins
Agarose Bead Technologies (ABT)
High-performance agarose resins for enhanced bioprocessing efficiency
Drug discovery is the process by which potential new therapeutic entities are identified using various scientific techniques (1).
Although it is the first step in pharmaceutical projects, drug discovery remains a long and costly process in which less than 1% of drug candidates are successful (2). For this reason, optimization in drug discovery is a major focus in the pharmaceutical industry.
In drug discovery, the identification of inhibitors of therapeutic targets is critical. One of the most important screening techniques is affinity selection-mass spectrometry (AS-MS), which facilitates the identification of small molecule ligands that act as the aforementioned inhibitors.
The optimization of this method implies the immobilization of therapeutic targets in agarose resins such as ABT Agarose Resins. For example, we can find a recent study in which the immobilization of ubiquitin-specific protease 1 (USP1) in agarose resins has boosted drug discovery in several cancer diseases (3).
USP1 is an enzyme involved in the regulation of DNA repair and is overexpressed in lung cancer, osteosarcoma and colorectal cancer, where it contributes to tumor progression and chemoresistance (4). Inhibition of USP1 has been shown to promote apoptosis in cancer cells. Thus, the immobilization of USP1 in agarose resin and its association with potent small molecule inhibitors represents a relevant improvement in pharmaceutical projects involving cancer treatments.
The methodology is simple and consists of coupling His-tagged recombinant USP1 to a Ni-NTA agarose resin, such as ABT's Nickel NTA agarose resin, in a column. A mixture of potential inhibitor molecules is then passed through the resin. The specific inhibitors bind to USP1 while the nonspecific molecules flow out. Once the resin contains only the bound USP1-inhibitor complex, it must be eluted and processed for subsequent mass spectrometric analysis and inhibitor identification (Figure 1).
All in all, as reported, the use of affinity resins is a good choice to improve and optimize the drug discovery phase in pharmaceutical companies in a time and cost-effective way.