Domainex Researchers Identify Small-Molecule Inhibitors of TBK1/IKKepsilon Affecting IL-17 Signaling
News Nov 05, 2012
Domainex Ltd. 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".
Scientists Develop a Synthetic Solution to Combat Dwindling Supply of Cancer and HIV DrugNews
Supplies of a promising drug for cancer, HIV and possibly other diseases is dwindling, and scientists have struggled to extract more from the marine creatures who produce it. Now, chemists have a synthetic solution.READ MORE
Arsenic Trioxide Could Extend Lives of Patients with Aggressive Brain CancerNews
Arsenic trioxide could be a powerful therapy that could extend the lives of certain glioblastoma patients by as much as three to four times the median expectation.READ MORE
Gilead Company Wins FDA Approval for CAR T Cancer Therapy for Treatment of Adult LymphomaNews
Kite’s Yescarta™ (axicabtagene ciloleucel) becomes first CAR T therapy approved by the FDA for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy.READ MORE
Comments | 0 ADD COMMENT
Annual Conference on Antimicrobials and Drug Resistance
Sep 24 - Sep 25, 2018
1st Alpine Winter Conference on Medicinal and Synthetic Chemistry
Jan 28 - Feb 01, 2018