The OTAVA MolGluesLike Compounds Library is a scientifically curated collection of 871 small molecules designed to enable the discovery and development of molecular glues — a groundbreaking modality in drug discovery that stabilizes or induces protein-protein interactions (PPIs).

These specialized compounds have the potential to redefine therapeutic strategies by targeting previously “undruggable” proteins, offering exciting opportunities in areas such as oncology, immunology, and neurodegenerative disease research.

What Are Molecular Glues?

Molecular glues are monovalent small molecules that can promote ternary complex formation by either:

• Inducing neomorphic PPIs (bringing together two proteins that do not typically interact), or
• Stabilizing existing, weak PPIs (reinforcing biologically relevant complexes).

Their ability to modulate protein function — by mechanisms such as targeted protein degradation or allosteric pathway tuning — makes them powerful tools in drug discovery, especially for targets lacking classical ligand-binding pockets.

Library Design and Scientific Excellence

Our MolGluesLike Library has been meticulously assembled using a multi-parameter optimization strategy that ensures:

• High biological relevance
• Excellent drug-like properties
• Broad chemotype coverage for PPI modulation

1. Rigorous Filtering and Compound Integrity

• PAINS and reactive group removal to eliminate false positives and unstable compounds.
• Frequent hitter exclusion: Compounds with known non-specific activity against kinases, phosphatases, or proteases have been removed to increase screening accuracy.

2. Optimized Physicochemical Properties

• Topological Polar Surface Area (TPSA): 20 – 110 Ų
• Hydrogen Bond Donors (HBD): Fewer than 3
• Calculated LogP (cLogP): Less than 6
• Molecular Weight (MW): Below 600 Da
  These parameters align with guidelines for cell permeability, solubility, and favorable pharmacokinetics — critical for intracellular PPI targeting.

3. Advanced 3D Descriptor Profiling

Our selection process integrates 3D molecular descriptors to prioritize compounds with geometry favorable for PPI interfaces:

• Plane of Best Fit (PBF)
• Normalized Moment of Inertia (NMI)
• Flexibility, globularity, and sphericity This ensures spatial compatibility with concave and planar surfaces often found in protein interfaces — ideal for glue-mediated binding.

4. Cell Penetration and Biological Viability

All compounds in the library are selected for intracellular accessibility, a fundamental requirement for successful modulation of protein-protein interactions in live cells.

5. Structural and Scaffold Diversity

To support wide-ranging research applications, the library features high scaffold diversity, enabling exploration across various PPI interfaces, protein families, and therapeutic mechanisms.

Applications and Opportunities

• Targeted Protein Degradation (TPD)
• Oncology drug discovery and immune modulation
• Neurodegenerative disease models
• Chemical biology and functional proteomics
• Exploration of novel E3 ligase biology and PPI networks

This library provides an exceptional platform for both phenotypic screening and rational glue discovery, including CRBN- and DCAF-based degraders, non-degradative stabilizers, and emerging self-associating glues.

Collaborate with Us

Whether you're focused on high-content screening, rational PPI targeting, or next-generation degraders, our team can help you:

• Access the full MolGluesLike Library
• Customize compound subsets based on your biological targets
• Design collaborative screening campaigns tailored to your discovery pipeline

⇒ Contact us today to accelerate your research with a world-class molecular glue library

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References:

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9. Li, F., Aljahdali, I., & Ling, X. (2022). Molecular glues: Capable protein-binding small molecules that can change protein–protein interactions and interactomes for the potential treatment of human cancer and neurodegenerative diseases. International Journal of Molecular Sciences, 23(11), 6206. https://doi.org/10.3390/ijms23116206
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11. Sasso, J. M., Tenchov, R., Wang, D., Johnson, L. S., Wang, X., & Zhou, Q. (2022). Molecular glues: The adhesive connecting targeted protein degradation to the clinic. Biochemistry, 61(10), 1044–1057. https://doi.org/10.1021/acs.biochem.2c00245
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13. Shi, H. (2024). Molecular glues and molecular glue degraders: Mechanisms, design, and therapeutic applications. Transactions on Materials, Biotechnology and Life Sciences. https://doi.org/10.62051/r1m5q711
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