Kallikrein 6 Targeted Library

Kallikrein related peptidase 6 (Klk6) is a secreted serine protease that is abundantly expressed in the central nervous system, with highest levels in the brain stem and spinal cord, and at significant levels in other clinically significant brain regions, including the hippocampus, frontal lobe, substantia nigra, subthalamic nucleus and thalamus. In addition, Klk6 is also highly expressed in oligodendrocytes and is associated with demyelinating conditions. Kallikrein 6 (KLK6, hK6, Bssp, Klk7, PRSS18, PRSS9, SP59, kininase-releasing enzyme-related peptidase 6) plays an important role in various physiological processes. Given the dense expression of KLK6 in human brain and spinal cord, there is a strong interest in its potential role in central nervous system diseases. Disorders of KLK6 activity diseases have been observed at cancer and neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis. Oligodendrocyte-derived Klk6 can operate as an autocrine or paracrine rheostat, or brake, on pro-myelinating signaling serving to regulate myelin homeostasis developmentally and in the adult. Therefore, small-molecule compounds that modulate kalilrein 6 activity may have a significant therapeutic potential.

BOC Sciences has developed a kallikrein 6 targeted library (648 compounds in total) containing drug-like compounds with predicted inhibitory activity against KLK6.

Figure 1. Distribution of all members of the human kallikrein family at different sites of the central nervous system (CNS). (Mella, C.; et al. 2020)

Kallikrein 6 Targeted Library Design

At BOC Sciences, two receptor-based methods: pharmacophore screening and molecular docking are employed to carefully design this library:

1. Firstly, we have constructed six pharmacophore models with different pharmacophore features and excluded volume combinations (defined on hydrogen atoms of the amino acid residues of the substrate-binding site) using crystal of kallikrein 6 with inhibitor
2. BOC Sciences drug-like compound collection is then used to screen against these models, and also docked in the same crystal structure
3. In this step, the top-scored compounds generated by the pharmacophore screening are crossed with top-scored compounds obtained with docking
4. Finally, we carefully evaluate intermolecular hydrophobic contacts and hydrogen bonds with key substrate-binding sites residues

Kallikrein 6 Targeted Library Characteristics

BOC Sciences’ kallikrein 6 targeted library includes nearly 648 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 Kallikrein 6 Targeted Library characteristics

Features of Kallikrein 6 Targeted Library

• 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. Schematic representation of the KLK6 self-regulation and the major effects of it functions on brain physiology. (Mella, C.; et al. 2020)

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 Kallikrein 6 Targeted Library design at competitive prices for global customers. Personalized and customized services of Kallikrein 6 Targeted 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!