Projects per year
Kynurenine 3-monooxygenase (KMO) is a candidate drug target for Huntington’s disease (HD) and other neurodegenerative disorders, but known inhibitors are not brain permeable. Here, nineteen new KMO inhibitors have been identified. One of these (1) is neuroprotective in a Drosophila HD model but is minimally brain penetrant in mice. The prodrug variant (1b) crosses the blood brain barrier. Release of 1 in the brain lowers 3-hydroxykynurenine (3-HK) levels, a toxic metabolite linked to neurodegeneration. Prodrug 1b will advance development of targeted therapies against multiple neurodegenerative and neuroinflammatory diseases in which the KP 1 likely plays a role, including HD, Alzheimer’s disease, and Parkinson’s disease.
|Early online date||24 Jul 2019|
|Publication status||Published - 2019|
Research Beacons, Institutes and Platforms
- Manchester Institute of Biotechnology
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- 1 Finished
Manchester Synthetic Biology Research Centre for Fine and Speciality Chemicals
Scrutton, N., Azapagic, A., Balmer, A., Barran, P., Breitling, R., Delneri, D., Dixon, N., Faulon, J., Flitsch, S., Goble, C., Goodacre, R., Hay, S., Kell, D., Leys, D., Lloyd, J., Lockyer, N., Martin, P., Micklefield, J., Munro, A., Pedrosa Mendes, P., Randles, S., Salehi Yazdi, F., Shapira, P., Takano, E., Turner, N. & Winterburn, J.
14/11/14 → 13/05/20