Renin Targeted Library

The Renin (REN, HNFJ2), also known as REN and angiotensinogenase, is involved in arterial vasoconstriction and the body's renin-angiotensin-aldosterone system (RAAS), which mediates the volume of extracellular fluids (blood plasma, lymph and interstitial fluid). Renin activates the renin-angiotensin system (RAS) by cleaving angiotensin produced by the liver, producing angiotensin I, which is further converted into angiotensin II by ACE, the angiotensin-converting enzyme found mainly within the capillaries of the lungs. An over-active RAAS causes vasoconstriction and retention of sodium and water, and these effects lead to hypertension. Renin is able to regulate the body's mean arterial blood pressure, and renin inhibitors can therefore be used for the treatment of hypertension.

BOC Sciences has developed a renin targeted library to offer 1001 compounds with predicted inhibiting activity against REN.

Figure 1. Renin-angiotensin system (RAS)-dependent and -independent pathways. (Nabi, A.; Suzuki, F. 2010)

Renin Targeted Library Design

BOC Sciences supports the combination of ligand-based and receptor-based virtual screening methods to maximize the number of active compounds identified during the screening process. We employ machine learning (Bayesian statistics, artificial neural networks and k-nearest neighbor algorithm (k-NN)) and molecular docking to carefully design this unique library:

1. Firstly, we cluster the known REN inhibitors into eight clusters
2. Then, the compounds in each cluster are classified as active or inactive using k-NN based on molecular fingerprinting to generate a more homogeneous set, and randomly divided into training and test sets. Different molecular descriptors such as LogP, molecular weight, number of rotatable bonds, number of rings, number of hydrogen donors and acceptors, PSA, fingerprints, topological descriptors are available for both approaches
• The training set is applied for development and parameterization of artificial neural network and Bayesian model
• The test set is used to validate Bayesian models and neural networks
3. Finally, the top-scored compounds obtained by applying machine learning methods are crossed with the top-scored compounds obtained by molecular docking. Our team carefully evaluate intermolecular hydrogen bonds and hydrophobic contacts with key amino acid residues of active site of renin to select the compounds that eventually entered the library.

Renin Targeted Library Characteristics

BOC Sciences’ renin targeted library includes a diversity of 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 Renin Targeted Library characteristics

Features of Renin 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 diagram for the in vitro binding properties of renin and prorenin molecules to the immobilized (pro)renin receptor. (Nabi, A.; Suzuki, F. 2010)

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