Accelerating Early Stage Drug Discovery with PAM

Bryan C. Webb

The Problem

In order to accelerate drug discovery, many labs are increasingly looking to the use of predictive modeling and proteomics to accelerate early stage research.  At $1M/day, the costs and risks are enormous and the path can be up to 15 years long.  Cost-effective ways to reduce the time-to-market are needed that can eliminate R&D bottlenecks and reduce reliance on the small, yet high-cost pool of suitably qualified analytical scientists (PhDs) in the pharma technology sector.


Early stage drug discovery labs are being squeezed by their management to do more with less time and resources.  Current analytical lab-based solutions are costly in terms of equipment and staff, and this process creates what can be significant time delays that may also impact results.  What is needed is a simple Protein Aggregation Monitor (PAM).  A PAM could quickly (in seconds vs. 20 minutes via HPLC) measure relative protein size or protein-protein interactions that involve size changes.

Using a PAM, a lab would quickly be able to pre-screen all candidate solutions for the presence of aggregates and thus more efficiently discard those candidates that do not pass the initial test for aggregation.  Alternatively, simple kinetic studies that look at inhibitor efficiency or similar size dependent parameters of interest could be done right at the bench with minimal training in instrumentation and using only a very small sample (conserves expensive protein resources).  This would leave the central analytical lab to concentrate on testing the more promising candidates with their sophisticated and time consuming techniques to provide a more in-depth analysis where needed and dramatically reducing this key bottleneck in the discovery process.

The Solution

A simple-to-use and low-cost PAM, sitting right on the bench, would permit a lab to pre-screen far more samples to quickly weed out unsuitable candidates and thus reduce the load on the expensive central analysis facilities.  It could provide aggregation results in seconds, while the software is operated by a typical lab technician without additional highly qualified supervision.  Using a very small volume (2μl) and requiring no fluorescent tag, a PAM further reduces tedious sample preparation time and costs.

Compared to traditional analytical instruments, a low-cost, easy-to-use PAM-type tool can save significant amounts of capital and lab time.  A typical PAM would combine proven laser light scattering technology with proprietary smart software algorithms and a novel flow cell design to provide an easy-to-use tool for every lab.

A Simple Technology Comparison

                                     PAM                             Traditional

Footprint                       150 cm2                        600 cm2 or larger

Budget                          Operational                   Capital Budget

Location                        Lab Bench                    Analytical Lab

Operator                       Technician                    Analyst (PhD)

Sample Usage             2 μl                               12 to 200 μl