Most of biological processes would not be possible without protein-protein interactions (PPIs). Human interactome is estimated to include over 600,000 PPIs, and only a small part of them have been studied. PPIs are associated with a growing number of diseases and have gained great interest in pharmaceutical research, offering attractive opportunities for therapeutic intervention. Targeting protein-protein interactions is a promising strategy because PPIs are involved in many cellular processes. However designing molecules that interfere with the formation of protein complex is one of the recent challenges in drug design.
Of all the identified targets associated with human disease, more than half are considered to be difficult to modulate by traditional small-molecule drugs that meet Lipinski's "Rule of Five" (Ro5), with PPIs being important examples. These hard-to-drug targets often have large, featureless, highly lipophilic or highly polar and highly flexible binding sites. The search for intracellular hard-to-target drugs with oral bioavailability is a difficult task and often requires the discovery of corresponding ligands in unknown chemical space outside of Ro5.
To address this complexity, BOC Sciences has created a library of large but not "greasy" molecules of PPI modulators that accord with the “Rule of Four”, and contain compounds with functional groups that interact with important Arg, Trp, and Tyr residues.
Figure 1. PPI modulators binding to interacting proteins and interaction interfaces. (Zeeshan, Z.; Ghulam, M. 2028)
Rule of Four-based PPI Focused Library Design
BOC Sciences’ Rule of Four-based PPI focused library includes a diversity of therapeutically relevant compounds that are carefully selected from our proprietary collection of HTS compounds to meet the parameters listed in the table below.
Table1. The summary of the BOC Sciences Rule of Four-based PPI Focused Library characteristics
| Parameter | Value |
| MW | ≥400 |
| Number of H Donors | 0-4 |
| Number of H Acceptors | ≥4 |
| Number of Rings | ≥4 |
| Number of Rotatory Bonds | ≥4 |
| Number of Heavy Atoms | 25-40 |
| Fsp3 | ≥0.4 |
| CLogP | ≥4 |
| TPSA | ≤150 |
Features of Rule of Four-based PPI Focused Library
- Similar to known PPI inhibitors from TIMBAL database
- This Rule of Four-based PPI focused library has been designed based on selected sp3-enriched compounds to ensure their complexity and 3D-diversity
- All PAIN and reactive compounds are excluded from selection by internal filter applications
- Structurally diverse subset, with the option to favor hit discovery
- Structural analogs available for SAR studies
- All compounds are continually updated
- Compound cherry-picking service is available
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 Rule of Four-based PPI Focused Library design at competitive prices for global customers. Personalized and customized services of Rule of Four-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!
Reference
- Zeeshan, Z.; Ghulam, M. Protein-Protein Interactions as Potential Targets of Drug Designing. Advances in Biochemistry & Applications in Medicine. 2018.
