Human Presequence Protease (hPreP) Agonist Library

A neurotoxic peptide β-amyloid (Aβ) is associated with the development of Alzheimer's disease (AD). The accumulation of amyloid-β inside mitochondria promotes the production of free radical and the activation of the apoptotic pathways. The accumulation of Aβ within the mitochondria and scape perpetuates the activation of free radical production and apoptotic pathways. HPreP is responsible for the degradation of mitochondrial amyloid-β peptides in neuronal cells and is therefore an attractive target for increasing Aβ protein hydrolysis, especially for Alzheimer's disease drugs.

BOC Sciences has developed a library of hPreP agonists to develop small molecules that modulate hPreP function to enhance degradation and clearance of mitochondrial small unstructured peptides including Aβ.

Figure 1. hPreP binding site for compounds. (Vangavaragu, J.; et al. 2014)

Human Presequence Protease (hPreP) Agonist Library Design

At BOC Sciences, two approaches: pharmacophore screening and Bayesian models are employed to design the library which contains compounds with predicted hPreP activating activity:

1. Firstly, one part of compounds is selected by a five-point pharmacophore of our drug-like green collection
2. Secondly, another part of the compound library is selected via using Bayesian model based on fingerprints and molecular descriptors
3. Finally, the top-scored ligands are selected from the above two screenings, of which 30% are overlapped

Human Presequence Protease (hPreP) Agonist Library Characteristics

BOC Sciences’ human presequence protease (hPreP) agonist library includes nearly 1,050 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 Human Presequence Protease (hPreP) Agonist Library characteristics

Features of Human Presequence Protease (hPreP) Agonist Library

• Physicochemical properties of compounds in the library are related to BBB permeation
• 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

Figure 2. Selective synthesis of imidazole scaffold and selected molecular targets of human PreP activators. (Vangavaragu, J.; et al. 2014)

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 Human Presequence Protease (hPreP) Agonist Library design at competitive prices for global customers. Personalized and customized services of Human Presequence Protease (hPreP) Agonist 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!