MDM2-p53 Interaction Inhibitors Library

p53 is a potent tumor suppressor and is an attractive target for cancer therapy because it can be functionally activated to eradicate tumors. The gene encoding p53 protein is mutated or deleted in half of all human cancers, thereby inactivating tumor suppressor activity. MDM2 protein is the core negative regulator of p53 that maintains the cellular levels of p53 at low levels in normal cells. Mutation of the TP53 gene account for 50% of all human cancers. In the malignancies with wild-type TP53, p53 function can be inhibited by other mechanisms. Recently, synthetic small-molecule inhibitors have been developed which target the small hydrophobic pocket on MDM2 to which p53 normally binds. Scientists have conducted clinical trials of MDM2-p53 antagonists against different types of cancers. Small molecule inhibitors designed to block the MDM2-p53 protein-protein interactions (MDM2 inhibitors) have been used as a new cancer therapeutic strategy. In recent years, effective, selective and potent MDM2 inhibitors have been successfully obtained and seven such compounds have been advanced into early stage of clinical trials for the treatment of human cancers.

BOC Sciences is committed to designing mall-molecule inhibitors (MDM2 inhibitors) to block the MDM2-p53 protein-protein interaction.

Figure 1. Schematic representation of the domain structures of p53, MDM2 and MDM4. (Merkel, O.; et al. 2017)

Library Design

At BOC Sciences, our experts have established a high-throughput virtual screening method based on molecular docking approach to generate this library:

1. A receptor-based virtual screening process is created based on X-ray data for the complexes: 4ZYF
2. The compounds in the HTS compound collection have been pre-filtered using BOC Sciences' internal filters and then docked at the active site. Moreover, we have considered a variety of H-bond constraints: HOH323, HOH302, VAL93, GLN72
3. Finally, 22,000 potential MDM2-p53 interaction inhibitors selected with computational chemistry and virtual screening techniques are generated successfully

MDM2-p53 Interaction Inhibitors Library Characteristics

• 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
• All of these compounds with Tanimoto index ≥ 0.85
• Compound cherry-picking service is provided

Figure 2. Drugs that interact with the MDM2/p53 binding pocket. (Merkel, O.; et al. 2017)

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 MDM2-p53 Interaction Inhibitors Library design at competitive prices for global customers. Personalized and customized services of MDM2-p53 Interaction Inhibitors 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!