Are you looking for your leads in the right place?

What leads to better candidates?

After 10 years of developing leads for clients at BioBlocks, we have identified a combination of factors that can light the way to substantially better candidates for preclinical optimization:

• High quality chemical matter

• Robust and versatile chemistry

• Structural information

• Carefully chosen reagent sets

The Leap-to-Lead™ platform

CFL: A Proprietary Next Generation Fragment Library

The Comprehensive Fragment Library (CFL) is a set of small, low flexibility, medicinally interesting fragments. This library originates from a starting set of >3 million potentially synthesizable virtual fragments designed from first principles to maximize exploration of target interactions. Extensive 3D clustering analysis allows broad coverage of chemistry space and provides an immediate follow-up strategy from any screening hit.

CFL designed for maximum diversity with med chem friendly properties

Characteristics

• Diverse collection of rigid, low molecular weight fragments designed from first principles

• Designed using our team’s deep medicinal chemistry expertise to meet very strict property criteria

• Enables access to ~ 3 million high value fragments with less than 19 heavy atoms

Unique 3D enabled diversity fragment screening set

Benefits

• Break out of the 2D world with new chemical matter

• Choose from thousands of related virtual alternatives for each fragment hit

• Gain a head start on hit to lead and IP

• Access novel, 3D structures even from commercial hits

Enhanced Fragment Screening with the CFL

Recent Presentations

FBLD_2016 Poster

MEDI_2017 Poster

BioBlocks/Cresset User Group Meeting

FBLD_2018 Poster

DOT_2019 Poster

New Chemical Matter

Our experience suggests that there is an enormous amount of new chemical matter still available for drug discovery especially when fragment methods are used. Novel fragments are perfectly situated to develop unique, patentable molecules. By controlling fragment properties from the beginning, better quality preclinical leads can be developed with greater chances for clinical success.

Connecting fragment hits to new IP

Even a well-known commercially available fragment leads to novel 3D analogs through Comprehensive Fragment Library clusters.

CFL Library Properties

Property Distributions

Library Format

• Solutions in DMSO arranged arrayed by mutual agreement

• Typical sample is 2-4 mg compound dissolved in 0.2 mL DMSO (200mM solution)

Library Novelty

• Independent expert evaluation shows minimal overlap with other fragment libraries

Syntheverse™

The Syntheverse™ is the Leap-to-Lead platform’s very large virtual library that provides useful, property-filtered compound sets. It enables our partners to identify alternative lead series and new hit to lead paths.

A US patent has been issued to BioBlocks for Syntheverse™ technology.
US9946847B2

How it Works

Providing access to over 500 billion compounds, the Syntheverse™ produces sets of diverse synthesizable products through precoded synthetic schemes and purchasable starting materials. Starting from an initial fragment or any synthetic compound, compound sets with predesignated properties are generated for additional selection by virtual screen or direct synthesis and assay. 

When queried with an active molecule, compounds are suggested which are synthetically accessible via one or more existing synthetic routes. Such output provides library design ideas for hit follow-up from screening or lead/scaffold hopping to novel series. 

The Syntheverse™ is a road map to every compound synthetically achievable

Benefits

• Improve access to currently synthesizable compounds

• Practice the art of the possible: discover your lead in the synthetically accessible universe of compounds

• Revisit your patent strategy by replacing common building blocks with new sizes and shapes

• Leap beyond the ordinary limits of imagination to optimize your lead

Improved Lead Optimization & IP Coverage

Capitalizing on the enormous numbers of synthesizable compounds

Our experience suggests that there are enormous numbers of new chemical compounds available for drug discovery even from known reliable reactions and truly commercially available starting materials. Starting from any individual compound or fragment, a tree of all synthesizable products can be generated. The full set of products is impractically large for enumeration. However, a high value subset can be selected from the Syntheverse using property and structure filters. Virtual screen evaluation and prioritization by synthetic ease generates a compound list for synthesis. For each compound selected, the tree provides the synthetic scheme.

Starting from a novel, proprietary compound or fragment, the Syntheverse generates a novel product tree. The compounds produced represent the accessible IP space available around the novel compound.

~100 million compounds from 64 reaction schemes

Case Study

Using the Syntheverse™ in a recent project provided steady improvement towards a Lead Series. Critically, for this project we retained valuable lead properties by exploring more options and making only those that fitted design criteria. Despite the fact that the initial scaffold was well-known, a patent application has been filed on a selected compound set from Run 2.