Integrins are an important class of transmembrane glycoprotein (GP) receptors consisting of alpha- and beta-subunits. During platelet activation, integrins are able to change their conformation (inside-out signaling) and outside-in signaling occurs, leading to platelet spreading, platelet aggregation and thrombus formation. Integrin αIIbβ3, the major membrane protein on platelets, mediates platelet aggregation by rapidly transiting from its resting to an activated state, in which it acts as a receptor for ligands that can bridge platelets together. A variety of studies have shown that many monoclonal antibodies, natural products and small peptides have shown inhibition of αIIbβ3 dependent platelet aggregation, and these antagonists have been tested preclinically and entered into large patient trials for the treatment of acute coronary syndromes.
BOC Sciences is dedicated to the rational targeting of integrinαIIbβ3, and has developed a proprietary library of integrin αIIbβ3 integrin.
Figure 1. The inactive conformation of the αIIbβ3 integrin. (Kerkhof, D.; et al. 2021)
Library Design
At BOC Sciences, our experts have established a high-throughput virtual screening method based on molecular docking approach to generate this library:
- A receptor-based virtual screening process is created based on X-ray data for the complexes: 2VDM
- 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: TYR122, SER123, ASN215, ASN215, HOH4069, SER225, ASP224. There are Metal ion coordination sites in the β3βI domain in unliganded-closed αIIbβ3 and liganded-open αIIbβ3
- Finally, 1,445 potential αIIbβ3 inhibitors selected with computational chemistry and virtual screening techniques are generated successfully
αIIbβ3 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 overview of inside-out signalling in platelets. (Kerkhof, D.; et al. 2021)
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
Figure 3. Schematic overview of outside-in signalling in platelets. (Kerkhof, D.; et al. 2021)
BOC Sciences provides professional, rapid and high-quality services of αIIbβ3 Inhibitors Library design at competitive prices for global customers. Personalized and customized services of αIIbβ3 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
