Challenges of HTS in early-stage drug discovery
Reflections from Stefan
“High-throughput screening (HTS) is much more than just, as very often associated, a numbers game and finding the needle in a haystack. It is a “par excellence” multi-disciplined team approach to identify the most relevant bioactive compound, the magic moment when for the first time a molecule shows a biological effect. It is important to pick the winners early and in very smart ways. You have to do HTS properly, then chance is on your side!
Therefore, you need as ingredients a great performing disease relevant assay, a very curated and diversified compound collection, smart screening and data analysis protocols as well, and most importantly a great team.
“SMART” = Screening for Molecules Acting on Relevant Targets”
At the core of the drug discovery process is the screening of hundreds of thousands of compounds with in-vitro assays using high-throughput methods. Time-sensitive and cost-effective strategies are decisive for the identification of validated hits with a specific pharmacological activity.
High-throughput screening (HTS) is a stepping-stone in the drug discovery pipeline. It is an evolving discipline and a process that consists of multiple synchronized automated steps involving handling large libraries of small drug-like molecules, transferring small quantities of liquids, incubation of the small drug-like molecules with either cells or proteins of interest in controlled temperatures, and the measurement of a pre-determined signal, such as fluorescence, luminescence or other, from the assay optimized for HTS. Each step could contribute to the systematic variation in the screening data.
The challenge is to distinguish truly biologically-active compounds from inactive and false positives.
The HTS process must be a disciplined approach that needs to be concomitantly flexible and tailor-made to set up the best hit finding strategy also for difficult target classes, via a synergistic approach between biology, chemistry, engineering and informatics.
At Axxam, we have a long history and proven experience in HTS, enabling us to support our clients during the early phases of drug discovery, from assay design to HTS campaigns, and even further during the hit-to-lead process. State-of-the-art screening stations, established criteria for quality control review and active identification, together with tailored screening campaigns and expertise are crucial elements for the success of a high-throughput screen, ensuring a reliable compound class and its advancement for later stages of drug discovery.
Screening, drug discovery, HTS, compound, data analysis, tailor-made, hit-to-lead, expertise, validated hits, quality, automation, chemistry, high-throughput, IC50, EC50, potency, selectivity, primary, 384, 1536
- Sanjeevani Tawde – Head of Operations & Program Management, Axxam GmbH
- Angela Molteni – Unit Manager, HTS / Automation, Axxam S.p.A.
Sanjeevani “Sanjee” Tawde has a Master’s degree in cancer biochemistry and an MBA in pharmaceutical management.
She has a decade-long experience in high-throughput screening (HTS), working at various CROs and pharmaceutical companies, road-mapping biochemical and cellular assays for several HTS campaigns, and organizing communication for an extensive cross-section of clients.
She currently works as the Head of Operations and Program Management at Axxam GmbH in Constance, Germany. Her responsibilities include budgeting, resourcing, planning, and executing HTS campaigns, along with overseeing of the organizational performance as a part the corporate-leadership team.
Angela Molteni is currently the Unit Manager of the HTS-Automation group at Axxam S.p.A. in Bresso, Italy, coordinating a team of 10 people, 4 automated robotic systems and following on average 20-25 screening programs per year. She has a Master’s degree in Molecular Biology and before joining Axxam in 2001, she gained experience in biochemistry and in the development of biochemical assays for HTS in pharmaceutical companies.
Her deep expertise in the high-throughput screening (HTS) field, have been consolidated in the last 15 years, executing HTS campaigns on biochemical and cellular assays, data analysis of screening campaigns and compound profiling activities, and acting as automation manager in programming and upgrading the robotic systems.