Poised Fragment Library

Fragment screening is an effective method to establish an initial point of drug discovery. However, for simple and small molecules, their chemistry is not simple. Quite the contrary, fragment hits may be difficult to follow in this case. Synthetic paths can be long and rigid which do not allow small specific changes to grow, link, or merge the hits. To address this, BOC Sciences have synthesized a library of compounds using a diversity of robust and versatile synthetic reactions. Our professional teams apply standard parallel chemistry to construct a library of analogs, helping to identify ‘poised’ bonds in a fragment.

Figure 1. How a poised fragment library is used to synthesize a follow-up library of analogues. (Cox, O. B.; et al. 2016)

Library Design

Poised fragments

Poised fragments are fragments synthesized from robust and versatile synthesis reactions and parallel chemistry is usually used to rapidly refine fragments into analog libraries. Our poised fragments have the following characteristics:

• Identify a poised bond in fragments allows deconstruction of compounds into more than one two synthons
• The binding activity can be increased significantly to allow for a series of measurement
• Robust reactions, which are tolerant to a wide variety of substrates, are conducted using multiple commercially available starting materials
• Accurate structural information of the ligand binding site can be obtained
• We generate reaction products in high yield which contain drug-like functions with no known toxicological moieties

Design of Poised Fragment Library

• To construct a high quality library, we analyze a large number of fragments assembled in-house to identify the existence of poised substructures and prevalent synthons
• We then select a subset containing more than 400 compounds to ensure diverse chemotype and poised sort
• Multiple molecular fingerprints are employed to deliver more than 200 clusters
• Compounds in our library are selected based on structural diversity and diversity of poised motif
• Additionally, we apply a number of filters in-house to ensure drug-like characteristic of fragment molecules in our library
• Further filters are applied to ensure that each compound can be compatible with various reaction
• Finally, a set of sophisticated algorithms are created to ensure that chemical diversity is maintained

Poised Fragment Library Characteristics

At BOC Sciences, the well-established library consist of more than 850 compounds covers accessible poised fragment space via using our selected reactions, which is the largest and most reliable source of high-quality fragments. We cooperate with leading experts in the field of FBDD to design and supply top-level fragment libraries, aiming to meet needs of each client.

Table1. The summary of the BOC Sciences Poised Fragment Library characteristics

Features of Poised Fragment Library

• No PAINS, REOS or toxic substances/unwanted functions: filtered by previously reported and internally developed pharmaceutical chemical filters
• The design principle is to allow fast, low-cost follow-up synthesis to provide quick SAR data
• The poised fragments contain at least one functional group and can be synthesized using robust, well-characterized reactions
• At BOC Sciences, the reactions are frequently used in parallel chemistry include amide coupling, Suzuki-type aryl-aryl coupling, aromatic nucleophilic substitution, synthesis of sulfonamides, ureas, reductive amination, etc.
• All fragment spaces are analyzed for poised-ness
• The library of our poised fragment hits can improve the potency into the sub-mM range while showing good ligand efficiency and detailed structural data
• Cherry picking service is available

Figure 2. Design of DSPL1 (A) scaffolds used to identify poised fragments. (Cox, O. B.; et al. 2016)

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
• Analytical data is provided

BOC Sciences provides professional, rapid and high-quality services of Poised Fragment Library design at competitive prices for global customers. Personalized and customized services of Poised Fragment 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!