Advancements in Drug Discovery: From Hit Identification to Efficient Lead Optimization
On May 20, 2026, Viva Biotech hosted a crucial webinar titled "Managing Complexity in Modern Drug Discovery: A Practical Approach to Integrated Screening Chemistry." This insightful session was moderated by Victoria Ouroutzoglou, the Associate Director of Business Development at Viva Biotech and featured expert insights from Dr. Bing Xia, Vice President and Head of Early Discovery Platforms, and Dr. Tim Dwight, Senior Director of Medicinal Chemistry/Business Development. During this roundtable discussion, the focus was placed on the significance of adopting integrated screening workflows that encompass medicinal chemistry to enhance scientific rigor in the early stages of drug discovery.
Dr. Bing Xia highlighted the importance of context in hit identification, underlining that this process is significantly influenced by the target in question. The strategy should begin with an analysis of the target's biological validation, tractability, and assay readiness, as well as structural information, protein availability, and existing intellectual property.
When quality structural data is available, techniques like fragment-based drug discovery or virtual screening can offer efficient pathways into the process. In scenarios where reliable functional or cellular assays exist, high-throughput screening (HTS) becomes a robust tool for evaluating biological activity across extensive compound libraries. For targets that are more challenging, affinity-based methods such as DNA-encoded libraries (DEL), active-site mapping, or surface plasmon resonance (SPR) are vital for addressing initial questions about druggability, particularly when protein access or assay availability is limited.
A notable approach discussed was Viva Biotech's V-DEL-facilitated target triage method. By fusing DEL screening results with protein chemistry expertise and AI-powered insights, this strategy aids in assessing ligandability and helps prioritize targets based on their suitability for drug discovery, especially for newly characterized or first-in-class targets.
Dr. Xia further pointed out that while primary screening results are instrumental, they represent merely the starting line. Moving forward with a hit requires a multi-faceted validation process that includes confirming purity, checking liabilities, conducting dose-response evaluations, and performing selectivity and cytotoxicity tests. Establishing a layer of validation is critical as it aids in distinguishing actionable hits from misleading candidates and assay artifacts.
Viva Biotech maintains a continually refined dataset on "promiscuous frequent hits" to support informed assessments. This internal resource, built on accumulated screening data, plays a pivotal role in decreasing the risk of promoting erroneous hits from one screening campaign to the next.
Upon successful hit validation, embarking on design-make-test-analyze (DMTA) cycles becomes crucial. Dr. Tim Dwight emphasized the importance of collaboration across various disciplines—medicinal chemistry, biology, and pharmacokinetics. These DMTA cycles typically follow a weekly rhythm to align with the primary assay workflows, thus enabling teams to formulate new hypotheses, refine designs, and prioritize compound selections comprehensively.
The contribution of tools such as structure-based design, ligand-centric structure-activity relationship (SAR) analysis, and AI/ML modeling can significantly streamline compound prioritization. The objective isn't only to generate designs but to rigorously test specific hypotheses and strategically determine which avenues to pursue, pause, or discard.
Interpretations of go/no-go criteria are critical in preventing programs from advancing too far without adequate proof of efficacy or feasibility. Vital aspects, including assay enablement, protein quality, and early considerations for chemistry manufacturing controls (CMC), significantly influence project decisions.
In summary, effective integration transcends the mere co-location of departments; it entails the seamless connection of pertinent data, expert insights, and decision-making checkpoints throughout the various discovery stages. By weaving together expertise in protein science, structural biology, and medicinal chemistry, Viva Biotech facilitates a continuous discovery workflow. This helps partners effectively transition from comprehending target sciences to reaching validated hits and ultimately achieving lead optimization with enhanced precision and efficiency.
Understanding Hit Identification
Dr. Bing Xia highlighted the importance of context in hit identification, underlining that this process is significantly influenced by the target in question. The strategy should begin with an analysis of the target's biological validation, tractability, and assay readiness, as well as structural information, protein availability, and existing intellectual property.
When quality structural data is available, techniques like fragment-based drug discovery or virtual screening can offer efficient pathways into the process. In scenarios where reliable functional or cellular assays exist, high-throughput screening (HTS) becomes a robust tool for evaluating biological activity across extensive compound libraries. For targets that are more challenging, affinity-based methods such as DNA-encoded libraries (DEL), active-site mapping, or surface plasmon resonance (SPR) are vital for addressing initial questions about druggability, particularly when protein access or assay availability is limited.
A notable approach discussed was Viva Biotech's V-DEL-facilitated target triage method. By fusing DEL screening results with protein chemistry expertise and AI-powered insights, this strategy aids in assessing ligandability and helps prioritize targets based on their suitability for drug discovery, especially for newly characterized or first-in-class targets.
The Necessity of Validation
Dr. Xia further pointed out that while primary screening results are instrumental, they represent merely the starting line. Moving forward with a hit requires a multi-faceted validation process that includes confirming purity, checking liabilities, conducting dose-response evaluations, and performing selectivity and cytotoxicity tests. Establishing a layer of validation is critical as it aids in distinguishing actionable hits from misleading candidates and assay artifacts.
Viva Biotech maintains a continually refined dataset on "promiscuous frequent hits" to support informed assessments. This internal resource, built on accumulated screening data, plays a pivotal role in decreasing the risk of promoting erroneous hits from one screening campaign to the next.
DMTA Cycles and Hypothesis-Driven Design
Upon successful hit validation, embarking on design-make-test-analyze (DMTA) cycles becomes crucial. Dr. Tim Dwight emphasized the importance of collaboration across various disciplines—medicinal chemistry, biology, and pharmacokinetics. These DMTA cycles typically follow a weekly rhythm to align with the primary assay workflows, thus enabling teams to formulate new hypotheses, refine designs, and prioritize compound selections comprehensively.
The contribution of tools such as structure-based design, ligand-centric structure-activity relationship (SAR) analysis, and AI/ML modeling can significantly streamline compound prioritization. The objective isn't only to generate designs but to rigorously test specific hypotheses and strategically determine which avenues to pursue, pause, or discard.
Integrative Approaches to Scientific Rigor
Interpretations of go/no-go criteria are critical in preventing programs from advancing too far without adequate proof of efficacy or feasibility. Vital aspects, including assay enablement, protein quality, and early considerations for chemistry manufacturing controls (CMC), significantly influence project decisions.
In summary, effective integration transcends the mere co-location of departments; it entails the seamless connection of pertinent data, expert insights, and decision-making checkpoints throughout the various discovery stages. By weaving together expertise in protein science, structural biology, and medicinal chemistry, Viva Biotech facilitates a continuous discovery workflow. This helps partners effectively transition from comprehending target sciences to reaching validated hits and ultimately achieving lead optimization with enhanced precision and efficiency.
Topics Health）
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