Tissue transglutaminase 2 (tTG2) is a multifunctional enzyme involved in extracellular matrix stabilization, cell adhesion, signal transduction, and protein crosslinking. It plays a pivotal role in various physiological processes, but its dysregulation has been implicated in multiple diseases, including celiac disease, fibrosis, cancer, and neurodegenerative disorders. Due to its involvement in disease progression, tTG2 is a prime target for drug discovery, yet the development of small-molecule inhibitors remains an underexplored frontier.
Advancing tTG2 Drug Discovery with OTAVA
The OTAVA tTG2 Inhibitor Library has been meticulously designed to address this gap by providing a chemically diverse set of compounds targeting tTG2 through reversible and selective interactions, moving beyond traditional inhibitor classes. Our library integrates cutting-edge chemoinformatics, structure-based design, and machine learning to ensure a broad exploration of tTG2 modulation strategies. The result is a high-quality collection of 1,765 compounds, including 196 fragment-sized molecules optimized for Fragment-Based Drug Discovery.
Key Features of the OTAVA tTG2 Inhibitor Library
✔ Comprehensive Compound Collection: A well-curated selection of 1,765 compounds with optimized drug-like properties and structural diversity.
✔ Fragment-Based Approach: 196 compounds with high ligand efficiency making them ideal for FBDD-driven hit expansion and lead optimization.
✔ Multiple Targeting Strategies:
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Active-Site Inhibitors: Targeting the catalytic Cys277 residue with reversible covalent and non-covalent scaffolds.
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Allosteric Modulators: Compounds designed to regulate the open/closed conformational states of tTG2.
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Protein-Protein Interaction Inhibitors: Disrupting tTG2-integrin and tTG2-fibronectin interactions to modulate ECM remodeling and cancer metastasis.
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GTPase Modulators: Interfering with nucleotide-binding sites to regulate intracellular signaling.
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Deamidation Inhibitors: Preventing gliadin peptide modification, relevant for celiac disease treatment.
New Expansion and Customization Options
✔ Access Novel, IP-Friendly Structures: Explore innovative chemical spaces with CHEMRIYA™, OTAVA’s AI-driven molecular expansion platform.
✔ Custom Synthesis & Optimization: Any selected molecule can be synthesized and delivered within 4-8 weeks, ensuring seamless integration into research pipelines.
✔ Flexible Screening Strategies: Compatible with biophysical assays (SPR, ITC), enzymatic screening, and cell-based functional studies, enabling tailored hit validation approaches.
Examples and Screening Strategies
The OTAVA tTG2 Inhibitor Library is highly versatile and can be applied in various drug discovery and biomedical research programs:
✔ Cancer Research: Screening for inhibitors that block tTG2-mediated epithelial-mesenchymal transition (EMT), metastasis, and chemoresistance in solid tumors.
✔ Fibrosis Studies: Identifying small molecules that prevent excessive extracellular matrix deposition in liver, lung, and kidney fibrosis models.
✔ Celiac Disease Modulation: Testing deamidation inhibitors to block tTG2-driven gliadin modification, reducing immune system activation.
✔ Neurodegenerative Disorders: Evaluating compounds that inhibit tTG2-mediated protein crosslinking in Huntington’s and Alzheimer’s disease models.
✔ Enzymatic Assays: Using high-throughput screening to assess compound interactions with tTG2’s active site and allosteric binding sites.
✔ Biophysical Techniques: Applying Surface Plasmon Resonance (SPR) and Isothermal Titration Calorimetry (ITC) to confirm binding affinity and kinetics.
✔ Cell-Based Functional Studies: Measuring the effect of inhibitors on cell adhesion, migration, and ECM remodeling in relevant disease models.
✔ In Vivo Validation: Testing lead compounds in preclinical models of cancer, fibrosis, and inflammatory diseases to assess therapeutic potential.
Unlock New Therapeutic Possibilities
The OTAVA tTG2 Inhibitor Library represents a next-generation resource for drug discovery, opening new avenues for the development of first-in-class therapeutics targeting tTG2-driven diseases. Whether you are exploring cancer, fibrosis, celiac disease, or neurodegeneration, our diverse and customizable compound library provides a powerful foundation for innovative drug design.
Contact us today to discuss library access, customization, and collaborative screening strategies tailored to your research needs.
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