2D Similarity-based Nuclear Receptor Ligand-Based Library

Nuclear receptors (NRs) are involved in a wide range of physiological critical functions, and constitute an important class of drug targets. NRs can be divided into three groups. The first is the classical and most widely characterized group of receptors that are essential for steroid hormones, thyroid hormones and vitamins A and D, all of which are essential for homeostatic control of endocrine system. The second class are orphan nuclear receptors, which are structurally related to nuclear hormone receptors but lack known natural ligands. The third class of NRs includes adopted orphan nuclear receptors.

BOC Sciences has employed and optimized a ligand-based virtual screening approach to build the nuclear receptor ligand-based library. Our team assists in the discovery of new NR ligands by providing comprehensive manually curated data on NR ligands and bound-structures pharmacological profiles.

Figure 1. Structural and functional organization of nuclear receptor superfamily. (Germain, B.; et al. 2006)

Library Design

BOC Sciences is able to generate a ligand-based library by performing a 2D fingerprint similarity search against nuclear receptor bioactivities recorded in the database.

a. Preparation of receptor structures

We have used the internal coordinate mechanics (ICM) method to construct hydrogen atoms and missing heavy atoms, sample polar hydrogens to optimize the hydrogen-bonding networks during the process of conversion

b. Generation of nuclear receptor ligand database

Our teams convert the compounds to 3D representation by ICM conversion program. Bond order, tautomeric form, stereochemistry, hydrogen atoms and protonation state are automatically assigned. The database includes more than one hundred known ligands: agonists, antagonists and selective nuclear receptor modulators

c. Ligand docking simulations

ICM docking program is established to optimize ligand internal coordinates in a grid potential maps of receptors

d. Virtual ligand screening

Ligand database is docked into each protein structure, and the highest scoring pose for each ligand is refined and re-scored. Ultimately, our library collects a variety of human nuclear receptor ligand binding domains for virtual screening and selective analysis of NR ligands

2D Similarity-based Nuclear Receptor Ligand-Based 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
• Compound cherry-picking service is provided

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 2D Similarity-based Nuclear Receptor Ligand-Based Library design at competitive prices for global customers. Personalized and customized services of 2D Similarity-based Nuclear Receptor Ligand-Based 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!