Scientific Solutions | Hit Identification

Fragment Based Drug Discovery

From high-quality starting points to optimized leads, we unite fragment screening, structural biology, computational chemistry and medicinal chemistry to keep your program moving forward .

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Sygnature laboratory setting handling a microplate, demonstrating hit identification process in drug discovery.

Supporting Your Research

Drug discovery using libraries of small molecule fragments with molecular weights of typically ≤300 Da offer s an effective route to hit identification for a wide range of biological targets.

Sygnature Discovery’s fragment screening platform is built to help you find high-quality starting points and progress them with confidence. We combine a purpose-designed fragment library with integrated biophysics, structural biology, computational chemistry and chemistry to tailor each campaign to your target, your biology, and your program goals.

Our in-house fragment library has been carefully engineered to maximize the likelihood of identifying tractable hits. It is curated for optimal chemical space and shape coverage, and fragments are selected for high “sociability” to support efficient progression through follow-up chemistry. Recent library expansions have been pocket-docked and machine-learning – scored against a panel of 50 diverse therapeutic target pockets to ensure practical relevance.

With substantial experience across complementary fragment-screening technologies, our teams routinely apply FBDD to demanding targets such as nucleotide-binding proteins and molecular glue programs. From initial screening strategy to hit validation and evolution, we move your program forward with speed and clarity.

Our Novel Fragment Library

Sygnature’s in-house fragment library is designed to deliver tractable hits that are straightforward to evolve. Our poised fragments include clear points of diversity for derivatization, and the collection contains small analogue sets around key functional groups to enable rapid early structure–activity relationship (SAR) exploration. Structural links between the fragment collection, the Sygnature Lead Finder library, and selected commercial sets support SAR-by-catalogue, keeping momentum high after fragment hit identification.

Tiered structure to support different screening routes

The library is organized into two tiers to better enable a range of approaches to FBDD :

Tier 1 is the complete library for high throughput biophysical screening, providing maximum diversity
Tier 2 is curated sub-decks selected from Tier 1, formatted to support lower throughput methodologies, providing either higher sensitivity or direct structural enablement
A complementary covalent fragment set is also available

Built-in flexibility for your program

This tiered approach lets you tailor hit finding to your target biology and available platforms. Typical workflows include:

High throughput biophysical binding assay, followed by confirmation through XRC or NMR
XRC or NMR screening, followed by affinity determination using a technology such as SPR, SpS, or MST

Providing this flexibility enables the prioritization of elements such as diversity or immediate structural enable, and the application of the best assay type for each target.

multi-well plate used for high throughput fragment screening in fragment based drug discovery

Fragment Screening Workflow

We deliver high-quality fragment hits through a robust and fully traceable workflow that connects technologies, libraries, and expertise. Every stage is integrated to provide clear visibility from start to finish, enable effective FBDD programs that keep projects moving decisively forward.

Assay Development and Pilot Screen

Identify screening concentration and potential hit rate.

Primary Screen

Select the initial hit list

Affinity Determination

Analyze binding behavior and
potency in depth.

Hit-repurchase + Closer Analogues

Hit Confirmation/Affinity Determination

Rapid SAR and confirmation of hits, including orthogonal assays where needed.

Ongoing DMTA cycles

Fragment Follow-Up

Fragment follow-up is driven by structure-based design and rapid SAR generation to move efficiently from initial hits to optimized leads.

Using crystallography, NMR or cryo-EM structures, our CADD teams apply methods such as mixed-solvent molecular dynamics and water mapping to reveal adjacent pockets and prioritize high-affinity growth opportunities. We control molecular properties using efficiency metrics such as LE and LLE. Fast, high-confidence structural feedback, including PanDDA analysis where appropriate, guides iterative AI supported design. Structural links to Sygnature and commercial screening libraries enable accelerated “near-neighbor” SAR-by-catalogue.

When bespoke synthesis is needed, our poised fragments help select high-value vectors for elaboration. Our long-established high-throughput chemistry capability enables rapid exploration of those vectors, ensuring momentum through ongoing DMTA cycles.

Why Choose Sygnature Discovery for FBDD Support?

We provide a complete, integrated platform for fragment-based drug discovery, designed to move you from hit identification to lead optimization with speed and rigor. You gain a purpose-built fragment library and a cross-discipline team that united structural biology, biophysics, CAD, and chemistry together with full traceability and fast feedback.

Our end-to-end support spans protein production and structural biology, including X-ray crystallography and NMR, biophysical fragment screening using SPR, MST and DSF, crystallographic screening, computational chemistry with AI-enabled design, and medicinal chemistry supported by high-throughput SAR generation. Whether you need a full FBDD campaign or targeted support at a key stage, we tailor the approach to your target and objectives.