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MONASH FRAGMENT PLATFORM

 

About

The Monash Fragment Platform MFP provides academic and commercial researchers with access to fragment-based drug discovery technologies for their therapeutic targets. The facilities are located at the Monash Institute of Pharmaceutical Sciences – Australia’s largest and most successful pharmaceutical institute.

MFP screening uses our high-quality, in-house fragment library designed to maximise chemical space coverage and enable rapid hit optimisation. Screening cascades are tailored for each target and can be performed using a variety of techniques including NMR spectroscopy and surface plasmon resonance (SPR).​

Working with us

    • Collaborative research

      We collaborate with academic investigators from Australian and international institutes on drug discovery programs aimed to improve public health and tackle emerging diseases. Assay development and preliminary screens are are provided to substantiate grant applications and we can help with grant writing. Please contact us to explore the potential of your drug target using the MFP.

    • Fee for service

      We provide fully assisted FBDD technologies from screening to lead development at competitive rates. Services include NMR, crystallography, SPR and medicinal chemistry. Our SPR facility can also be accessed for antibody-antigen and protein-protein interactions. 

    • Consultancies

      The MFP has experts able to help you with your research needs. We can advise on feasibility studies, assay development, screening modalities and avenues for hit optimisation. Contact us to schedule a one-on-one discussion – consults are available to all Monash students and staff and other public and private research organisations. 

    Key instrumentation

    • Bruker 600 MHz CryoProbe​ NMR spectrometer
    • Australian Synchrotron​ access
    • BIAcore S200 SPR
    • BIAcore T200 SPR
    • Two SensiQ Pioneer Fragment Edition SPR
    • MicroCal ITC200 isothermal calorimeter
    • Reveleris X2 flash chromatography system
    • Genevac EZ2 parallel evaporator
    • Shimadzu NexaraX2 LCMS

    Expertise

    ​The MFP team provides expertise in structural biology to support rational drug design​; biophysical characterisation to quantify the affinity and kinetics of binding interactions; medicinal chemistry and chemoinformatics for the design and synthesis of elaborated fragment hits.

    Specialist services

    Library design

    Our platform provides high quality screening sets designed to maximise chemical space coverage while maintaining chemical tractability for hit optimisation. Physiochemical, size and PAINS filters eliminate undesirable attributes prior to compound selection. Importantly, we validate all compounds in our screening sets for identity, purity and aqueous solubility by NMR spectroscopy and LCMS, thereby greatly reducing the incidence of false positives. In addition to our standard screening sets we have more than 6000 additional fragments and near neighbours available for testing. This enables libraries to be tailored for specific classes of targets if desired. The extended collection includes analogues of primary screening compounds to enable rapid hit follow-up.

    Assay development

    Screening cascades are tailored for each target. We work with you to determine which primary and secondary screens best suit your target, considering such factors as protein size, stability and production yields and the availability of natural substrates or inhibitors. SPR assay development can be provided as an independent service or to establish conditions prior to fragment screening. MFP can assist with protein production, including isotope labeling for protein-detect NMR. Selective labeling strategies can be designed for protein-detect NMR of large proteins.

    Fragment screening

    Multiple screening formats are available including ligand-detect NMR and SPR. Fluorine NMR is available as an additional detection method. HSQC NMR can be used to validate hits and identify binding sites. Crystallography services are available to initiate a structure-based drug design program using the Australian Synchrotron at Monash.

    Hit optimisation

    We offer structure-activity relationships (SAR) by catalog compound sourcing. And our library is designed such that all compounds in our screening sets have at least 10 analogues available for immediate purchase. This enables us to establish SAR in a rapid and cost-effective manner prior to commencing a chemistry program.

    Lead development

    MFP is located within the Monash Institute of Pharmaceutical Sciences, which provides ready access to medicinal chemistry expertise to elaborate fragment hits into higher affinity lead compounds. MFP uses our highly efficient REFiL strategy, enabling the rapid exploration of chemical space without the need for a large chemistry program. By combining the efficiency of parallel chemical synthesis with off-rate screening by SPR we can rapidly synthesize libraries of fragment analogues in plate-format to explore SAR along an expansion vector to identify new binding interactions.​

    Hit optimisation

    Contact

    • Martin Scanlon

      Director                                                                                                         T +61 (3) 9903 9540                                                                                 E martin.scanlon@monash.edu

    • Bradley Doak

      Senior Scientist
      T +61 (3) 9903 9117
      E bradley.doak@monash.edu

    Location