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

Parameter	Value
MW	100-260
ClogP	-1.5-4.5
Number of Rotatable Bonds	≤4
Number of H Donors	≤4
Number of H Acceptors	1-5
Number of Rings	>0
Compounds with ‘undesirable’ functionalities	Removed
Fsp3	0-1
TPSA	<115 Å2
Number of Aromatic Rrings	0-3
Number of Heavy Atoms	8-19

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!

Reference

Cox, O. B.; et al. A poised fragment library enables rapid synthetic expansion yielding the first reported inhibitors of PHIP(2), an atypical bromodomain. Chemical Science. 2016. 7(3).

Online Inquiry

Services Based on the Chemical Library Design Platform

BOC Sciences has rich experience in working with global customers in custom library synthesis of compounds and generating small to medium-sized libraries of target compounds. Our knowledge in generating a large number of target molecules in a remarkably shorter time enables quick biological screenings for affinities. With the target properties in mind, we deliver target molecules, by applying our extensive knowledge in drug discovery.

Our mission is to provide clients with a professional chemical library design platform. Empowered by high-quality services and effective research solutions, we are committed to helping customers achieve effective and successful research goals.