CRELUX is an experienced, reliable and established service provider of drug discovery solutions. To balance speed, risk and cost of your drug discovery project, CRELUX provides a number of customized hit-finding, -confirmation and -optimization services. In these programs, you can choose between a variety of tailor-made combinations of our screening, crystallography and chemistry platforms. In close communication with you we will select and provide the best set of technologies to solve your task according to your specific needs.
We have a versatile technology platform and a very broad expertise in disease relevant and challenging protein targets. Here we just highlight a few of them.
Fragments are screened at CRELUX by SPR, MST, DSF, NMR or MS based methods. We have an in-house rule of 3 compliant 3500 fragments carefully selected with regard to chemical diversity. The molecular weight ranges from 130 to 317 and averages at 189 Da. Our screening process allows us to use the in-house library or any client fragment selection.
Subsequently, fragment hits will be validated with an orthogonal method and subjected to crystallization.
Based on available knowledge about the target we use in silico techniques with the goal to derive a predictive model applicable our virtual High Throughput Screening (vHTS) technology, and perform either a docking or a pharmacophore alignment. A database of approximately 6 Mio compounds consisting of commercially available drug-like small organic molecules is screened for the identification of candidate molecules.
Resulting from the vHTS experiment the top scoring compounds are further processed by the team of an experienced modeler and a medicinal chemist. Compounds are acquired and tested subsequently in vitro. The standard package of virtual hit compounds provided for evaluation in our biophysical assay systems (INTRACT) usually comprises around 210 to 300 compounds and results typically and 10-30 hit molecules.
For Hit validation target proteins are produced with our highly parallelized expression and purification platform. We are continuously advancing innovations in protein expression to generate stringently controlled premium proteins – for use in assays, screening, diagnostics or crystallization. Decades of cumulated protein expertise enable us to provide you with difficult to produce proteins like membrane proteins, secreted proteins, or nuclear receptors as well as metabolic enzymes, proteases, epigenetic proteins, phosphatases and kinases.
Screening hits are re-screened for determination of the exact KD values. In the next step, the best compounds or fragments are advanced into crystallography, where their binding to your target will be quantified.
To facilitate SAR analysis all hits from biophysical screening will undergo evaluation by X-ray crystallography. A final package of our Hit finding and validation package will include a set of confirmed hit compounds or fragments from different scaffold families which are structurally validated.
The WuXi AppTec drug discovery platform supports clients throughout the drug discovery process, utilizing expertise in synthetic chemistry, medicinal chemistry, in vitro biology, DMPK and program management. We collaborate closely with our international customers, ranging from pharma and biotech to academia and non-profit institutions, to rapidly advance programs towards key inflection points and milestones. WuXi’s peer-recognized synthetic chemistry and medicinal chemistry expertise and best-in-class, fully integrated drug discovery and development platform enable clients’ programs to progress seamlessly from target through to clinical development and beyond. We work closely with our partners to establish strategy, customize resources with tailored solutions, and guide project execution to deliver on goals. For more information, please contact us or visit the WuXi AppTec website.
Epigentics describe the transcriptional regulation of gene expression by enzymes that are modifying DNA or Histones. This process represents the underlying molecular machinery for any personalized therapeutic approach and has made its way from “just another molecular mechanism” to a strong focus of global drug research.
CRELUX has the world’s largest collection for crystallization of epigenetic targets. Moreover we have established a number of biophysical and cell based assays geared towards epigenetic analysis. No matter if it is readers, writers or erasers of epigenetic signals - we have it all.
Contact us directly for any epigenetic target request.
Benefit from our kinase expertise. We offer the largest collection of readily available kinases for complex structure determination. Get our highly pure crystal-grade protein or send us your ligand and get the complex structure back.
In addition, numerous kinase assays are available. KD values can be determined with MST.
With our partner INTANA, you can get access to FCCS (fluorescence cross-correlation spectroscopy) and can get on and off rates for your ligands. The full 520 human kinase panel is available with a labeled compound or with 266 kinases in a competition assay with any label free compounds.
The following kinases are available from CRELUX (please click here to download XPRESS portfolio).
A number of kinases are available as wild type structures as well as disease relevant mutants like the EFGR kinase domain G719S, T790M, L858R and the T790M/L858R double mutant. Please contact us directly if you are interested in disease relevant mutants.
CRELUX also offers crystallization and X-ray structure analysis for biologics including antibodies, Fc or Fab fragments. Complexes of Fab fragments in complex with the antigen provide the most accurate method of epitope mapping and mode of action determination. Furthermore it enables rational, knowledge based optimization. The X-ray structures also support your IP and are useful for patent filing, the drug approval process or your marketing team.
Despite an increasing number of publically available protein structures membrane proteins are very likely still the most challenging target family for crystallization. The major bottleneck is certainly the production of soluble material for crystallization screening. Crelux makes use of its proprietary expression tools to improve stability and homogeneity of recombinantly expressed membrane proteins. CRELUX has established various parallelized expression and solubility screening tools to identify solubly expressed constructs and is actively working on a number of membrane protein targets. CRELUX scientists have solved and published membrane protein structures during their academic careers.
A major challenge for nuclear receptor crystallization is their frequent requirement of co-factor activator or repressor peptides or proteins. Co-expression and co-purification systems established at CRELUX help to significantly enhance the yield of soluble protein material and allowed us to having solved a high number of nuclear receptor structures with agonist, antagonist or mixed action ligands.