'Drug discovery is terribly expensive, just to find out how one drug could or could not work and all its side effects' -Henry Markram
Drug development is not a cake walk. It takes lot of patience and resources. Path of drug development is full with hurdles. Gaining a clear understanding of how a drug works before it enters clinical trials is the intelligent route to drug discovery and could increase the likelihood for drug success. Mechanistic knowledge is certainly worthwhile before entering the uncertain world of clinical trials—this knowledge can increase the chances for drug approval, saving money, time and, most importantly, the lives of patients.
Mechanism of Action tells us how a drug works. Mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. The MOA can occur on the cell membrane, within the cell, or outside the cell. Since molecular targets bind to receptors, enzymes, or ion channel at the target site, the MOA can either be receptor mediated or non-receptor mediated. MOA studies and their need co-exist with each other. The reason why we as scientists need MOA studies is because:
We, at Dabur Research Foundation (DRF), have the expertise to undertake detailed mechanistic profiling of test products by study of various key markers involved in different therapeutic areas by multiple in-vitro assays. Techniques such as quantitative Polymerase Chain Reaction (qPCR) and ELISA come in handy for the purpose. But, Mechanistic profiling can be a tedious job. Few years back, we realized that this time consuming process can be simplified with more accuracy and thus, at DRF, we have made the task simpler. With the help of extensive panels and Multiplex platform for analysis in different sample types, we have tried to reduce the time and efforts that go in delineation of mechanism of action.
Delineation of mechanism at molecular level is performed using Multiplex platform. It is built by robust and well known Luminex xMAP technology. The Luminex Magpix™ (multi-analyte profiling) technology enables estimation of levels of multiple analytes (upto 50) relevant in various conditions, using just 25µL of sample. We can simultaneously detect different analytes offering significant cost saving and increased amount of information with limited sample adding value to early discovery research. xMAP technology is, designed to simultaneously detect and quantitate multiple secreted proteins (e.g., cytokines, chemokines, and growth factors) or expressed genes. The high-throughput technology produces results comparable to conventional assays such as ELISA and qPCR with greater efficiency and throughput. Luminex xMAP (Multi- Analyte Profiling) technology enables scientists to measure multiple proteins in a single well. It combines advanced fluidics, optics, and digital signal processing with innovated microsphere technology to deliver multiplexed assay capabilities.
Multiplex platform offers multiple advantages over the conventional methods such as:
We offer plethora of Panels that are useful for Mechanism study:
Panels are available for all major species such as human, rat, mouse, canine models. Multiplexing using xMAP technology is suitable for different matrix types such as cell culture supernatants, lysates, tissue homogenates, saliva, urine, plasma etc. Additionally, panels can also be customized to cater to the specific requirements of end user.
Graphically, Mechanistic Profiling may be summarized as
To conclude, Mechanistic profiling helps in determining the clinical safety and act as a benchmark for newer drugs before their release in the market.