Caseinolytic Protease ClpP Targeted Library

The caseinolytic protease proteolytic subunit (ClpP) is a serine protease that plays an important role in proteostasis of eukaryotic organelles and prokaryotic cells. Especially, human ClpP plays a key role in mitochondrial protein quality control system by removing damaged or misfolded proteins in mitochondrial matrix, thus ClpP can affect the virulence and infectivity of many pathogens. ClpP has emerged as an attractive and viable option that can tackle pathogen fitness. Moreover, overexpression of ClpP and other mitochondrial proteolytic machines is consistent in various cancers.

Aiming to develop compounds that target activation or inhibition of ClpP, BOC Sciences has developed a ClpP targeted library (825 compounds in total) containing drug-like compounds with predicted inhibitory activity against ATP-dependent Clp protease proteolytic subunit.

Figure 1. Cycle of ATPases associated with diverse cellular activities ClpP complex. (Moreno-Cinos, C.; et al. 2019)

Caseinolytic Protease ClpP Targeted Library Design

BOC Sciences has supported two receptor-based approaches: pharmacophore screening and molecular docking to carefully design this library:

1. First, a four-point pharmacophore model with excluded volume (on hydrogen atom of the amino acid residues of the active center) is developed based on of crystal of ClpP with N-formylmethionine
2. Then, the top-scored compounds obtained from pharmacophore screening are further docked in the same crystal
3. Finally, compounds are selected by applying docking score cut-off filtering included docking, inspection of intermolecular hydrogen bonds and hydrophobic contacts with key active sites residues, the catalytic triad Ser97, His122 and Asp171 in particular

Caseinolytic Protease ClpP Targeted Library Characteristics

BOC Sciences’ caseinolytic protease ClpP targeted library includes nearly 826 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 Caseinolytic Protease ClpP Targeted Library characteristics

Features of Caseinolytic Protease ClpP 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. Structure of the full E. coli ClpP tetradecamer and the ClpP monomer. (Moreno-Cinos, C.; et al. 2019)

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 Caseinolytic Protease ClpP Targeted Library design at competitive prices for global customers. Personalized and customized services of Caseinolytic Protease ClpP 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!