Domainex Researchers Identify Small-Molecule Inhibitors of TBK1/IKKepsilon Affecting IL-17 Signaling

05 Nov 2012
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Domainex Ltd., a UK-based drug discovery company, has developed a number of chemical series with potent and selective activity against two closely-related kinases TBK1 and IKKepsilon. IL-17 mediated signaling is known to induce the expression of cytokines and other effectors that can cause a variety of immunological diseases such as psoriasis and Chronic Obstructive Pulmonary Disease (COPD). Domainex researchers are now the first to report that small-molecule inhibitors of TBK1/IKKepsilon are able to affect IL-17 signaling. These results suggest that the Domainex inhibitors may have utility in a wide range of clinically-important diseases that have great unmet medical needs.

Recent clinical studies reported in The New England Journal of Medicine by Lilly and Amgen have shown that neutralizing anti-IL-17 monoclonal antibodies can have a major impact on psoriasis (Leonardi et al. 2012 and Papp et al. 2012 respectively). The demonstration by Domainex that small-molecule drugs targeting IKKepsilon can inhibit IL-17 signaling indicates that these compounds have great clinical potential in this disease and other important settings.

Domainex has developed three series of drug-like compounds, each series having inhibitors with high potency and selectivity against other kinases. The lead compounds have good metabolic properties and the Company is now driving these compounds forwards towards a clinical candidate.

Domainex's Research Director, Trevor Perrior, said: "Domainex, in collaboration with The Institute of Cancer Research, has previously shown that its inhibitors of TBK1/IKKepsilon have activity against a variety of cancer cell-lines. Domainex has also demonstrated that its inhibitors are very potent blockers of interferon-beta production in immune cells, showing the compounds may have utility in diseases such as lupus. The latest finding that our TBK1/IKKepsilon inhibitors can also inhibit IL-17 signaling suggests that the compounds are also of potential use for treatment of other major diseases such as psoriasis and COPD. Domainex has recently obtained funding from the government-backed Biomedical Catalyst programme to explore the use of its inhibitors of IKKepsilon in COPD."

Eddy Littler, CEO of Domainex, said: "The latest results showing the activity of Domainex's TBK1/IKKepsilon inhibitors against IL-17 signaling reinforces the fact that this project is of very high interest to pharma. Indeed Domainex is already in discussion with a number of potential partners with a view to them helping us to progress the programme to the clinic, and fully exploit its enormous potential. We are also grateful for the Biomedical Catalyst award that will enable us to extend our work to COPD, and help us fully exploit our intellectual property on inhibitors of TBK1 and IKKepsilon".

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