Service Partners

Domainex offers a wide range of drug discovery services within its laboratories in Cambridge; including medicinal and computational chemistry, biochemical assay and cell-based assay development, hit identification and in vitro DMPK. For additional areas of drug discovery, not covered internally by Domainex; Domainex has partnered with a range of companies to support your needs. This includes:

Pharmidex

Pharmidex Logo

Domainex and its closely located partner, Pharmidex, have built up an excellent working relationship over a number of years; ensuring speed and efficiency at all stages of your discovery programme.

Pharmidex provides an extensive range of ADMET technologies aimed at optimizing potential new medicines for drug development risks using both preclinical and human prediction data. Together with a wealth of knowledge and experience in CNS, CV, respiratory and inflammatory discovery programmes, Pharmidex can aid rapid progression and improvement in the probability of success of potential new medicines.

Pharmidex's offering includes, but is not limited to:

  • Blood distribution and protein binding
    • Plasma protein binding - human & most species
    • Blood partitioning - human & most species
    • Tissue partitioning human & most species
    • Blood to brain partitioning - human & most species (fraction unbound)
  • Cell Permeability and transporter interactions
    • Cell permeation - passive and Pgp mediated (MDR/MDCK)
  • CYP interactions
    • Inhibition in singly-expressed human P450 inhibition
    • Inhibition of Human P450 in microsomes (probe drugs via LC-MS/MS)
    • Time dependent inhibition of human P450s
    • Induction- Human P450 induction in hepatocytes
    • Reaction Phenotyping -Human P450Â isoform specific metabolism reactive metabolism glutathione trapping
    • Metabolite identification in biological samples

Prof. Laurence Pearl - The University of Sussex

An X-ray or NMR structure of the target protein, preferably with a bound ligand, is considered to be a highly desirable feature of any drug discovery project. To meet this need, Domainex works with its scientific founders, who are world-leaders in structural biology, to deliver structural information to its clients. This information can then be used in virtual hit screening or to further guide medicinal chemistry efforts in later stages of drug discovery programs.

Following the production of drug target protein using Domainex’s Combinatorial Domain Hunting technology, Domainex works with Prof. Laurence Pearl FRS (Professor of Structural Biology at the University of Sussex), in order to deliver high resolution crystal structures of the target protein of interest. 

The Pearl Laboratory is one of the UK's leading Structural Biology Groups, having determined more than 30 new protein structures in the last 10 years, including major drug development targets such as Hsp90 and the protein kinases GSK3beta, Ire1 and CHK2. They specialize in determining the structures and mechanisms of some of the most challenging proteins and complexes, and have been at the forefront in contributing to technical developments such as CDH.

Within the Pearl laboratories, the process of structure solution is separated into 3 phases:

The Process:

  1. Initial investigation consisting of:
    a. Eight sparse matrix screens (96 conditions each). Duplicated at 2 or 3 temperatures.
    b. Nanoscale sitting-drop vapour diffusion or under-oil microbatch formats available.
    c. Follow-up of plates over timescale of up to 1 month.
  2. Secondary investigation of up to 9 initial hits consisting of: 
    a. Multi-dimensional optimisation of initial conditions.
    b. Matrix microseeding in best 2 screens to increase number of hits.
    c. Follow-up over timescale of 1 month.
  3. Data collection and structure determination: 
    a. Test best crystals for diffraction.
    b. Data Collection on best crystals.
    c. Structure determination (Molecular Replacement or experimental phasing).
    d. Refinement and Building.

Once structural data is available, Domainex’s computational scientists are able to complete a virtual small molecule hit screen using its LeadBuilder software, to provide a focussed screening set of hit-like molecules against the drug target of interest.

Domainex will manage this entire process and maintain good communication links with the client at all stages, so that the project is seamlessly and efficiently delivered.

For more information on the use of Domainex’s Combinatorial Domain Hunting technology and follow up crystallography studies, please contact us.  Alternatively, please email laurence.pearl@sussex.ac.uk to contact Prof. Laurence Pearl directly.