Structural biology and drug discovery

Structure-activity relationship (SAR) analysis and its applications in drug discovery

Hetal Marble, Ph.D.

Head of Commercial, Immuto Scientific

Drug discovery is all about finding and perfecting novel compounds that can be utilized to treat diseases. The process can be labor-intensive, resource-intensive, and requires various specialists from several domains. Structure-Activity Relationship (SAR) analysis provides a systematic method for elucidating the connection between a compound's structure, chemical makeup, and biological activity. It is thus a crucial notion in the drug discovery process, and a primary method through with Immuto participates in co-development partnerships.

SAR analysis is predicated on the hypothesis that a target's molecular structure influences its biological activity. A molecular structure comprises its chemical composition, atomic arrangement, and molecular-level interactions. Researchers can improve the efficacy or decrease the toxicity of a target by altering its molecular structure. For a SAR analysis, the molecular structure is resolved in detail and across differing conditions, and then the target's biological activity is evaluated. The structure-resolved target is then bound to therapeutic candidates, the interactions and behaviors studied, biological activity is evaluated, and the causal link between structure and performance is established.

Understanding the molecular basis of biological activity is crucial for optimizing drug candidates, and SAR analysis provides a framework. Researchers can build more potent and selective molecules with enhanced efficacy and lower toxicity by elucidating the structural factors responsible for biological action. By using the guidelines provided by SAR analysis, scientists can rationally design novel drugs to enhance their efficacy and safety profiles.

While SAR analysis has been an important part of the drug discovery process for a long time, recent developments in technology and computational power have allowed for more extensive and accurate SAR analysis than ever before. One business that is at the vanguard of these developments is Immuto, which uses high-resolution protein footprinting to elucidate structures and find new medicines. Via Immuto's proprietary platform, we generate detailed, native-state structures at amino acid-level resolution for any protein or peptide, alone or in a complex, on an ultra-rapid timescale. By using this method, Immuto can efficiently screen a considerable number of targets and binders to improve their therapeutic potential.

Drug discovery using Immuto's technology also includes SAR analysis. Immuto's platform helps to optimize the molecular structure of novel compounds to increase biological activity and decrease their toxicity by utilizing SAR analysis via high-resolution structure. This strategy may drastically shorten the time it takes to find new medications, cut their development costs in half, and make them safer overall.

An example list of steps for Immuto's SAR analysis is below:

• Find a promising target that possesses the drives the desired biological or therapeutic process

• Examine the target's molecular structure using Immuto's proprietary protein footprinting platform and get residue-level higher-order structure

• Perform structure-based screening on the Immuto platform to evaluate binding sites and binding behavior of promising hits

• Support structural hit characterization with cell-based assays and functional screens to evaluate the hits' biological activity.

• The connection between the target, hits, and the activity of those hits can be deduced by analyzing the results from the structural and functional experiments.

• Based on hit binding sites and activity, determine the aspects of the target and binders that are responsible for its biological activity.

• Utilize the results of the SAR analysis to guide the development of new therapeutic candidates with improved structures.

• Assess the efficacy and safety characteristics of the newly synthesized assets and test them for biological activity.

• Repeat this procedure with minor chemical adjustments until a promising therapeutic lead candidate emerges.

SAR analysis is an important tool in drug development since it helps researchers deduce how a compound's molecular structure changes affect its biological activity. Immuto's use of cutting-edge technology to improve and speed up structural analysis is only one example of how the modernization of the drug discovery process is revolutionizing SAR analysis. By following this procedure, researchers can employ SAR analysis to improve the efficacy and safety profiles of potential new drug candidates. Minor adjustments to the structure of a compound can have significant effects on its biological activity, making this method especially relevant in drug discovery.

Immuto's SAR analysis and ultra-rapid structural evaluation allow the quick, rational screening of vast compound libraries to find the most promising candidates for further therapeutic development. SAR analysis and novel approaches for structural biology are projected to play an increasingly crucial part in the drug discovery process as technology advances, resulting in new and more effective treatments for a wide range of ailments.


Hetal Marble, Ph.D.

Head of Commercial, Immuto Scientific

Dr. Hetal Marble is Head of Commercial for Immuto Scientific, a boutique CRO focused on protein structural characterization and drug discovery. Dr. Marble has had varied and extensive experience leading life science businesses. She led diagnostic product management at Quanterix Corporation, where she launched Quanterix’s first diagnostic test for Alzheimer’s disease and directed product strategy and go-to-market for all clinical diagnostic and research services products. She also led companion diagnostics and biomarker development for the Center for Integrated Diagnostics at MGH where she grew the division’s in-house CRO into a multi-million dollar enterprise by translating novel technologies into clinical practice and leading precision biomarker strategies for clinical trials. Prior to her work at MGH, Hetal worked in business development, alliance management, and strategic product marketing for both Promega Corporation and Pall Biotech (a Danaher company), managing and growing burgeoning commercial territories into millions of dollars in revenue. Hetal is foundationally an experienced research scientist – she received her Ph.D. at Brown University, where her graduate work focused on development of biomarkers for lineage-specific stem cell differentiation - she is the holder of two U.S. patents emerging from that work. Hetal is active in the scientific community; she is the elected Chair of Diversity, Equity, and Inclusion for the Association for Molecular Pathology (AMP); she is a member of the 2022 Women in Bio (WiB) cohort of Emerging Executives; she served on the Pathology Informatics Collaborative Community (PIcc), a collaborative community of the US Food and Drug Administration; and she is a contributing author on precision medicine for the book Taking Care of You, a book on women’s health being published by the Mayo Clinic Press in October 2022.

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