Scientists at Aurelia Bioscience have been involved in the design and development of many drug discovery projects incorporating complex biology and implementing a suite of assays designed to identify “active” compounds and improve their biological properties.
These properties include potency, selectivity and cell penetration. This work has involved consultation with project and target biologists to determine the most appropriate assay for the initial screen and any subsequent assays that many be required to remove compounds with unwanted off target effects, cross-over to other target family members as well as false positive compounds i.e. those that are active as a consequence of interacting with the reporting technology rather than the target directly.
The project is designed initially to test a large number of compounds and identify those with desirable properties, followed by further assays designed to help build potency, selectivity and specificity and remove unwanted properties of the lead molecules. A description of our iterative screening service and deliverables are outlined in this section…..
Iterative Cyclical Screening (Lead Identification – LI)
Iterative Biology Screening in a Cyclical manner to clients chemical synthesis needs
Assay already developed by Aurelia Bioscience or client, pharmacologically characterised for compound testing and used regularly to screen compounds
Delivery of activity data generated on each compound in the assay of choice on a cyclical basis to XC50 level of screening e.g. weekly, bi-weeks or monthly. Compounds synthesised by client for an iterative test cycle at Aurelia Bioscience
We have mapped out a generic screening cascade here that gives some indication of the type of approaches we have adopted when putting together a project. A description of our project biology services and the deliverables are given in this section…..
Complete Drug Discovery Project – Assay Development to LI
Complete Discovery Project
Based around one target and involving assay development, validation, HTS, development of downstream assays, iterative screening of hits in cyclical manner against assays in the project cascade.
Fully developed and validated assays, data on all compounds screened in HTS assay and subsequent compounds synthesised and screened in appropriate assays. Consultancy and management of bio-reagent provision by sub-contractors as necessary. Frequent and detailed communication between Aurelia Bioscience and client.
We are very experienced in the respiratory and inflammatory biology research area and we have designed assays for other research areas including oncology and CNS-pain.
1,100 compounds IC50 against two cell-based assays then hits-to-lead SAR program in collaboration with chemistry CRO to generate novel IP
- Use their proprietary ‘Molecular Pharmacology’ software used to ‘weight’ biological pathways and interactions to identify key nodes essential for biological processes
- Identify hit compounds from a selected set of 1,100 compounds
- Screen the 1,100 compounds in two cell-based assays designed to detect antiproliferative effects then IC50 in both assays and a selective cyto-toxicity assay
- Generate a novel IP position with new compounds in a twelve month period