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Success Factors for Drug Discovery Journey From the Ground Up: Harnessing the Power of HTS

Scientist on June 28, 2023

This installment of Tech Snapshot® captures Axcelead’s integrated High-throughput Screening (HTS) platform, which ensures efficient hit identification, driving significant progress in drug discovery. In the pursuit of innovative therapeutics, identifying the right starting point is crucial. In this article, we highlight key success factors for drug discovery journey from the ground up.

Accessing a Diverse and High-Quality Compound Library

Successful drug discovery begins with identifying promising hit compounds. Axcelead offers access to the Pharma Origin Library, a collection of 1.5 million compounds including those with optimal characteristics for successful Hit-to-Clinical compounds such as low molecular weight and low lipophilicity.1 Additionally, Axcelead provides multiple focused libraries such as protein-protein interaction (PPI) targets, molecular glues, RNA targeted drugs and CNS targeted drugs. Furthermore, tailor-made focused libraries can be constructed by virtual screening. Leveraging these libraries gives you a competitive advantage in identifying hit compounds with favorable drug-like properties.

Invaluable Expertise and Data-Driven Approach

With a proven track record of over 700 successful HTS campaigns, Axcelead brings invaluable expertise to your drug discovery journey. Axcelead’s platforms cover various target classes, including enzymes, GPCRs, ion channels, transporters, nuclear receptors, PPI targets and nucleic acids. Axcelead specializes in new modalities like targeted protein degradation and RNA targeted drugs, enhancing small-molecule drug discovery. By combining deep scientific knowledge with a data-driven approach, Axcelead guides hit identification, target deconvolution, lead optimization and decision-making, increasing the likelihood of success at every step.

High-Quality Capabilities in Material Preparation and Assay Development

To conduct drug discovery successfully, high-quality materials and robust assay systems are crucial. Axcelead excels in these areas, with extensive experience in protein preparation and cell construction. Axcelead has developed numerous high-throughput assays, with the majority being built from scratch. From strategic planning to hit identification, Axcelead provides timely support, ensuring optimal material preparation and assay system construction. Axcelead’s clear vision for hit identification and subsequent profiling assays allows seamless assistance in the early stages of drug discovery.

Harnessing AS-MS and RapidFire-MS Technologies for Efficient Hit Identification

Axcelead excels in Affinity Selection-Mass Spectrometry (AS-MS) and RapidFire-MS technologies. AS-MS identifies binders for challenging targets, expediting hit identification. Axcelead efficiently screens and identifies hit compounds for projects targeting soluble proteins, membrane proteins, DNA, and RNA. For example, Axcelead found potent small molecule binders for FMN riboswitch RNA. These compounds were displaced with its natural ligand FMN. Axcelead can also provide multiple analysis including other biophysical methods as well as biochemical assays.

In addition, RapidFire-MS allows label-free screening by direct detection of analytes. With this technology, Axcelead empowers swift progress in drug discovery. For example, Axcelead has successfully conducted high-throughput screening for many projects using RapidFire-MS, including finding the first selective inhibitor of lactose dehydrogenase LDHB, which was clarified the allosteric binding mode using X-ray crystallography.2

By leveraging MS technologies effectively, we facilitate efficient hit identification and optimization.

Driving Phenotypic Drug Discovery through Comprehensive Screening and Mechanism Prediction

Phenotypic drug discovery is a straightforward strategy for discovering compounds with functional activities in disease models, facilitating the discovery of first-in-class drugs and drug repurposing. Axcelead possesses attractive libraries and state-of-the-art facilities for phenotypic drug discovery. Axcelead has conducted over 70 phenotypic screening campaigns using various cells, including iPSC-derived differentiated cells and primary cells. Additionally, we are continuously working on automating the process from cell culture to evaluation, aiming to enhance throughput and assay stability. Following hit identification, Axcelead is dedicated to predicting the mechanism of action through multiple target deconvolution methods, including biologically annotated compound libraries, chemical proteomics approaches, functional genetics with CRISPR technologies and phenotypic profiling through transcriptome analysis. Axcelead can accelerate your phenotypic drug discovery.

Seamless Integration of Biology and Chemistry for Informed Decision-Making and Streamlined Drug Discovery

At Axcelead, we understand the vital role of follow-up activities in achieving successful drug discovery. Axcelead’s HTS services seamlessly integrate with medicinal chemistry, optimizing hit compounds for potency, selectivity and ADMET properties. Through this Post HTS activity, medicinal chemists confirm or improve the SAR tractability and development potential in each chemotype, facilitating the expansion and prioritization of chemotypes for the lead generation stage. To prioritize hit compounds, we conduct biochemical assays for mode of action, selectivity and species differences and cellular assays for target engagement and efficacy confirmation. Advanced biophysical technologies confirm target interactions and provide valuable insights and structure-based drug discovery. Our tailored services and expertise empower informed decision-making and streamline drug discovery.

Incorporating HTS into the process of drug discovery, along with the seamless integration of diverse technologies, significantly enhances the likelihood of successfully identifying novel drug candidates. Contact us now to learn more about our reliable platform that turns innovative ideas into transformative therapies.



1) Brown, D.G. ”An Analysis of successful Hit-to-Clinical Candidates Pairs”J.Med.Chem. 66, 7101-7139, 2023.
2) Shibata, S., Sogabe, S., Miwa, M., Fujimoto, T., Takakura, N., Naotsuka, A., Kitamura, S., Kawamoto, T., Soga, T., “Identification of the first highly selective inhibitor of human lactate dehydrogenase B” Sci Rep. 11, 21353, 2021.