Why the Race to Drug the Undruggable Is Gaining Momentum
The article discusses the growing momentum in drug discovery efforts to target previously 'undruggable' disease-related proteins through innovative approaches like targeted protein degradation (PROTACs), uncovering hidden allosteric sites, advanced chemoproteomic workflows, and computational-experimental methods, driven by scientific advances in screening, structural understanding, and collaboration, as well as financial incentives favoring cost-effective small molecule drugs over biologics.
Despite the extensive progress toward finding cells hiding in our bodies known to influence disease, we only have medicines that act on a fraction of these targets. The evasive targets are often referred to as 'undruggable.'
Uncovering Evasive Targets
Research efforts to 'drug the undruggable' are wide-ranging and gaining momentum. Work is being done in small molecule drug discovery to:
- Open undruggable tumor targets using targeted protein degradation, such as with proteolysis-targeting chimera (PROTAC) or molecular glues
- Uncover hidden allosteric sites on disease-related proteins using combined computational and experimental approaches
- Expand covalent drug discovery beyond ligand-first approaches into electrophile-first approaches through use of robust chemoproteomic workflows
- Apply advanced NMR techniques to help in the structure-based design of drugs targeting small guanosine triphosphates (GTPases)
- Discover previously undetectable binding hot spots by using fragment-based computational and experimental methodologies
- Explore drug repurposing possibilities, such as the use of statins for inhibition of cancer proliferation
This push to expand the reach of small molecule drugs is fueled by many factors, both scientific and financial.
From a scientific standpoint, improved screening technologies mean new possibilities. Better target-site understanding has led to new disease targets. Improved computational chemistry techniques have opened more chemical space. Increased collaboration between biology and chemistry groups has helped teams work together to break boundaries.
From a financial standpoint, small molecule drug development remains relatively simple compared to the process of developing large-molecule biologics. With that simplicity comes cost efficiency that trickles down to the market, giving small molecule drugs both lower cost profiles and better patient accessibility.
But the endeavor to drug the undruggable is not without its obstacles. Companies still face a myriad of challenges. For example:
- Failure rates remain high. Every 10,000 hits synthesized and tested generate only 250 candidates. Of those candidates, around five to ten make it to trials.
- Process inefficiencies abound. Fragmented workflows and disconnected systems make it difficult to work efficiently and collaborate.
- Data liquidity remains low. Researchers and executives alike struggle to collect, find, and use their data to drive better decisions. By some estimates, up to 80% of R&D data are stuck in different systems and in different formats. As a result, as much as 60% to 80% of a data scientist’s time is spent cleaning and prepping data for use.
Dotmatics can help companies overcome these challenges by providing an end-to-end scientific R&D platform that connects best-of-breed applications that enable automation, analysis, and cross-discipline collaboration. The tools and solutions most needed for small molecule drug discovery are wrapped into the Dotmatics Small Molecule Drug Discovery Workflow.
Dotmatics' Small Molecule Drug Discovery Workflow:
- Supports cross-discipline discovery from hit and lead identification, through lead optimization, to candidate selection
- Provides fully integrated laboratory informatics software to capture experiments, molecules, samples, and assays
- Supports better decision making with tools for gathering, analyzing, and visualizing project data
To learn more about the ways Dotmatics can help companies in their endeavor to drug the undruggable, watch the on-demand webinar, "Reduce Risk, Cost and Time in the New Era of Small Molecule Drug Discovery."
Related
Data Management, Collaboration, and Workflow Optimisation: The Three Keys to Small Molecule Discovery Success
The article emphasizes that despite biologics' prominence, small molecule drug discovery is experiencing a renaissance driven by advances in screening, target exploration, and AI, but overcoming challenges like rising costs, data management, fragmented workflows, and CRO reliance requires success in three key areas: next-generation data management, enhanced cross-disciplinary research collaboration, and workflow optimization.
CIO.Inc: Can AI Finally Close the Gap Between Science and Software?
Alister Campbell, VP at Dotmatics, explains in CIO.Inc how AI is addressing the longstanding "last mile" challenge of translating scientific models into scalable software applications, enabling faster, more cost-effective development of personalized medicines and potentially revolutionizing patient access to safer therapeutics.
Addressing Inefficient R&D Workflows
The blog discusses how legacy, fragmented R&D systems hinder innovation in complex, multi-domain scientific research by creating silos and inefficiencies, and presents Dotmatics’ unifying platform as a comprehensive solution that integrates diverse tools, data, and teams to enable smarter collaboration, governed data use, and AI-driven automation for faster, more rigorous innovation.
Dotmatics Releases New Chemicals & Materials Solution Focused on Data-Driven Research to Accelerate Product Development
Dotmatics has launched its new Chemicals & Materials Solution, a data-driven R&D software designed to accelerate product development by enhancing project management, reducing duplication, and improving cross-organizational collaboration through simplified data intelligence and ingredient management workflows.
Dotmatics Supports Umicore Corporate R&D in Processing of Experimental Data
Dotmatics has been chosen by Umicore Corporate R&D to implement its R&D innovation platform, including an electronic laboratory notebook for over 200 users, to digitalize and standardize data processing across Umicore’s Catalysis, Energy & Surface Technologies, and Recycling divisions, thereby enabling researchers to efficiently generate data-driven insights and accelerate innovation in materials science, chemistry, and metallurgy over the next five years.
The Rise of Biotech: Why Smaller Companies Are Outpacing Big Pharma on Innovation
Smaller biotech companies are increasingly outpacing big pharmaceutical firms in new molecular entity approvals due to their greater agility, willingness to take risks, and freedom to innovate despite funding challenges, with over half of upcoming blockbuster drug launches expected from first-time launchers who face higher risks but also potential for significant success.