LFA1-ICAM1 Interaction Inhibitors Library

Lymphocyte function-associated antigen-1 (LFA-1) is an αLβ2 chain integrin expressed on the surface of endothelial cells that regulates the behavior of leukocyte by mediating the adhesion of leukocytes to other cells through its interactions to cell-surface ligands. LFA-1, also known as CD11a/CD18, is one of many integrins in the body, but its importance is derived from its unique presence in leukocytes. Many studies have shown the relation of LFA-1 and its primary ligand ICAM-1 (or CD54) with cancer through the function of lymphocytes and myeloid cells on tumor cells. lFA-1 can mediate leukocyte-tumor interactions. As the most important ligand for LFA-1, ICAM-1 is expressed on the surface of endothelial cells. The interaction between LFA-1 and ICAM-1 is involved in inflammatory response, and is therefore associated with inflammatory pathology and autoimmune diseases. Furthermore, ICAM-1 plays a crucial role in tumor dynamics, which can be independent of its interaction with LFA-1.

In view of this, BOC Sciences has a great interest in developing small-molecule oral inhibitors of the LFA-1/ICAM-1 interactions. We have created and characterized a structurally diverse collection of small-molecule inhibitors that can bind to the IDAS site of the α(L)I structural domain or to the MIDAS site of the β2 I-like domain.

Figure 1. Role of LFA-1/ICAM-1 interaction in the formation of the immunological synapse. (Pflugfelder, S. C.; 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: 3M6F, 2ICA
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: HOH408, HOH324
3. Finally, 1,779 potential LFA1-ICAM1 interaction inhibitors selected with computational chemistry and virtual screening techniques are generated successfully

LFA1-ICAM1 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. Schematic representation of the domain structure and conformations of LFA-1. (Pflugfelder, S. C.; 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 LFA1-ICAM1 Interaction Inhibitors Library design at competitive prices for global customers. Personalized and customized services of LFA1-ICAM1 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!