Domainex works with a wide range of organisations globally, including big pharma, biotech companies and academic groups. Examples of publically announced collaborations are described below, click on the links to go to the appropriate section:
Ark Therapeutics and Domainex have worked together to develop what are believed to be the first small molecule antagonists with nanomolar potencies for the neuropilin 1 ('NRP-1') receptor, which is considered to be a target of high potential in the treatment of cancer.
NRP1 is a receptor for vascular endothelial growth factor A165 (VEGF-A165) and the neuronal guidance molecule semaphorin3A(SEMA3A)2 with key roles in vascular and neuronal development. In endothelial cells, NRP1 enhances the biological signals of VEGF-A mediated by binding to its receptor vascular endothelial growth factor 2 (VEGFR2). NRP1 has also been implicated in tumour growth and angiogenesis; inhibition by a blocking antibody that prevents VEGF-A binding to NRP1 enhanced the antitumor effects of the inhibitory anti-VEGF-A antibody, bevacizumab in mouse xenograft models.
It is believed that a small molecule inhibitor of NRP1 function would be desirable, but inhibitors of protein-protein interactions are not trivial to develop. This notwithstanding, Domainex and Ark have worked together successfully to develop inhibitors of this interaction, using a peptidomimetic approach.
Medicinal Chemists at Domainex have collaborated with scientists at St George's University of London and the University of Manchester to develop novel chemical compounds known as Allergen Delivery Inhibitors (ADIs) which have the potential to become a new paradigm in the treatment of asthma. These compounds work by inhibiting proteases excreted by house dust mites that are believed to be one of the commonest causes of domestic allergy, and a major trigger for asthma attacks. This programme has successfully led to the nomination of a candidate drug (CD).
Throughout the programme Domainex has used its expertise in medicinal chemistry to design inhibitors of these proteases. Initial leads were optimised using Domainex's knowledge in inhaled drug design to generate compounds with the potential for use in a dry powder inhaler.
The project has been funded by the Wellcome Trust SDDI programme with Domainex playing a key role in securing > £ 4 million pounds worth of funding and ensuring that the project milestones were achieved. In addition to the nomination of a CD the programme has identified several developable back up compounds from chemically distinct and mechanistically distinct series allowing a robust patent portfolio to be generated.
In 2010, with Domainex’s support, Hypha Discovery successfully identified a pipeline of novel natural products that have significant activity against tumour cell lines.
Using Domainex’s LeadBuilder computational chemistry approach, Domainex successfully developed a series of low molecular weight anti-tumour agents based upon the structure of Hypha’s compounds produced by the fermentation of a tropical mushrooms.