Fragment Based Screening
Our FBS team has an in depth understanding of the properties required for the discovery and development of pharmaceutical compounds and biologics. We excel in combining effective hit generation solutions, such as fragment based screening, with Chemistry, Biology and DMPK services to drive drug discovery projects forward efficiently.
Our FBS capabilities include:
Screening of fragment libraries
- Ligand Observe NMR methods
- Saturation Transfer Difference (STD)
- WaterLOGSY (wLOGSY)
- Carr-Purcell-Meiboom-Gill (CPMG)
Library preparation of client or custom libraries
- Identity, solubility, and purity determination
- Automated smart pooling
- Positive control at regular intervals
- Diversity analysis
Follow-up analysis of hits
- Validation (follow-up of singletons)
- Rank-order; clustering of hits
Target Protein Generation
- Protein synthesis and purification
Target Preparation
- Screen design
- Sample optimization
- Experimental optimization
Complimentary Capabilities
- Orthogonal screening methods e.g. MST, DSF, HCS, SPR, TSA
- X-Ray Crystallography
- Computational Chemistry
- SAR design and synthesis to support hit optimization
- Biological Assays design and support
Fragment Library
The ChemPartner Fragment library has been specifically designed by computational and medicinal chemists to investigate as much chemical space as possible, within a specific range of molecular and physicochemical properties, making any hits discovered the ideal starting point for a drug discovery project.
Compounds in the ChemPartner library are selected on chemical diversity, good solubility in aqueous media and adhere to the ‘rule of three’ criteria:
- Molecular weight < 300
- clogP ≤ 3
- Number of hydrogen bond donors ≤ 3
- Number of hydrogen bond acceptors ≤ 3
Our unique fragment library of >2000 compounds is a combination of specifically selected fragments from:
- Commercial fragments
- Internal small molecule collections
- Fragments based upon FDA approved drugs
- 19F- containing fragments
- Covalent fragments
Screening external libraries
In addition to the ChemPartner fragment library, we are also able to use our FBS platform to screen:
- Client-provided fragment libraries
- Client-selected commercial libraries
- Custom commercial libraries
Additional capabilities
In addition to our FBS platform, ChemPartner is able to provide:
- NMR-based compound quality check
- Identity
- Purity
- Solubility
- Fragment pooling
- Randomized pooling
- Smart pooling
Versatile NMR Screening Methods
Our primary recommendation would be to conduct an initial fragment screen of a1000 member fragment library using NMR as the primary technique with confirmation of hits by orthogonal methods.
The first stage would be to screen the library using an NMR STD protocol, followed by further investigation of the hits identified using NMR wLOGSY or CPMG.
ChemPartner has access to a number of high field NMR instruments (600MHz or 700MHz) with cryoprobe technology.
Fragment hits using three NMR techniques
CPMG STD wLOGSY
Hits generated using the NMR platform could then be profiled further using orthogonal biophysical techniques such as MST, DSF, and SPR to determine Kd and kinetics.
SPR Equipment MST Trace
Hit Elaboration
ChemPartner is confident that our FBS platform will provide you with high quality hit compounds.
Our crystallography team can obtain high-resolution structures to guide the subsequent fragment elaboration.
In addition our skilled and experienced synthetic, medicinal and computational chemists can support the development of your hit molecules into clinical candidates.