Ligand-based PPI Focused Library

The strategies used to target the structure of a biomolecule in a drug development program depends on what it binds to, and the most common way to target a known modulator binding site is to introduce a ligand that competes to bind to the same site. However, many biomolecules do not have an obvious small-molecule regulator, but they interact with other biological macromolecules such as nucleic acids (DNA and RNA) or proteins. Protein-protein interaction (PPI) usually occurs in the surface region of two interacting proteins. The interaction between the two molecules can be obtained from many different smaller contacts on a larger surface area, rather than being concentrated in a smaller region (e.g., the binding site). This makes it difficult to target these interactions with small molecules because there are usually not enough interactions available for small molecules to bind strongly enough to compete with proteins larger than them. As a result, scientists often use a ligand-based approach to search commercial compound databases to find compounds with similar characteristics.

BOC Sciences has designed three screening sets of PPI modulators.

Figure 1. Predicted protein-protein interactions (PPIs) and their affected tissues. (Yu, H.; et al. 2020)

Ligand-based PPI Focused Library Design

BOC Sciences has utilized different techniques to design three libraries to screen out potential ligand-based PPI modulators to facilitate small-molecule high-throughput screening for PPI-related drug discovery programs.

• PPI Focused Library by Machine Learning

Our teams have designed a decision tree method containing multiple descriptors by comparing a dataset with protein-protein interaction inhibitors with a subset of many commercial databases through a machine learning approach that relies on classical QSAR descriptors. At BOC Sciences, our machine learning approach is able to predict potential PPI inhibitors

• PPI Focused Library by 2D Similarity Search

BOC Sciences extracts more than 3,000 drug-like screening compounds from the HTS compound collection by employing a 2D fingerprint similarity search towards the TimbalDB , 2P2IDB and iPPIDB. In addition, we have combined DB, Pubmed DB and ChEMBL DB to collect small organic compounds with activity in PPI-related assays towards various protein complexes

• PPI Focused Library by the Rule of Four

Aiming to find attractive PPI inhibitor-like compounds with full ”Rule-of-Four” compliance, our teams have createed a PPI modulators library. A molecule belonging to this space must obeys the following properties: MW ≥ 400 Da, cLogP ≥ 4, H-bond acceptors (HBA) ≥ 4, number of rings ≥ 4

Ligand-based PPI Focused Library Characteristics

• High diversity over the screening set: mean Tanimoto > 0.85
• Favorable physicochemical parameters and solubility requirements
• No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
• Bioactivity and safety confirmed by preclinical studies and clinical trials
• Structural diversity, medicinal activity, and cellular penetration
• Structural document, IC₅₀, and other chemical and biological data are provided
• All compounds are continually updated
• Compound cherry-picking service is provided

What We Deliver

• Delivered within 2 weeks in any customer-preferred format
• Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
• All compounds have a minimum purity of 90% assessed by ¹H NMR and HPLC
• Analytical data is provided

BOC Sciences provides professional, rapid and high-quality services of Ligand-based PPI Focused Library design at competitive prices for global customers. Personalized and customized services of Ligand-based PPI Focused Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!