CNS Drug Discovery

Innovative solutions to support CNS Drug Discovery

Disorders of the Central Nervous System (CNS) are a broad category of neurological conditions that affect the structure or functionality of the brain or spinal cord with devastating consequences. The treatment of brain diseases represents an important and growing area of unmet medical need. The growth of the neurodegenerative disease market is influenced by the rising prevalence of neurological disorders, the increase in average lifespan and the public awareness of mental health.

The CNS comprises the brain and spinal cord. Unlike most other organs, the brain is separated from the blood circulation by physiological barriers such as the blood brain barrier (BBB). The BBB functions as an important gatekeeper, regulating the traffic of small-molecules, ions, hormones and nutrients to the brain. Successful small-molecule treatments for CNS disorders must be designed to not only engage with the neurological target-of-interest, but also to have molecular properties designed to penetrate the CNS and reach the target-of-interest. By focussing on key physicochemical properties of molecules such as size, polar surface area, lipophilicity, pKa and the number of hydrogen bond donors, compounds can be designed which have a greater likelihood of reaching the brain.1,2 The integration of in silico, in vitro and in vivo data leads to improved understanding in order to better predict and optimise the brain exposure for neurological targets.

CNS Research at Domainex

Domainex has worked successfully on multiple CNS drug discovery programmes and is currently supporting clients who are developing novel CNS therapies by providing fully integrated research teams. Our medicinal chemists and computational chemists design and synthesise compounds according to physicochemical parameters consistent with delivery to the CNS to ensure your project has the best chance of success. In addition, our assay biologists offer a wide range of in vitro target engagement assays including for neuroinflammation, chemotaxis and microglial phagocytosis as well as bespoke screening cascades relevant to target activation. Find out more about our assay systems that aid in the fight against chronic neuroinflammation

Our protein scientists are able to produce and characterize proteins to support assay development and compound profiling, while our talented X-ray crystallographers can generate high-resolution structures to guide the design of your molecules.

We also collaborate with trusted strategic partners, on behalf of our clients, and use their complementary expertise to assess brain penetrability, in vivo/ex vivo target engagement and efficacy assays.

Parkinson’s UK Collaboration

Domainex currently has a major collaboration with Parkinson’s UK, the largest charitable funder of Parkinson’s research in Europe. The collaboration is focused on developing small molecule therapies targeting neuroinflammation that could slow the progression of Parkinson’s disease. Inflammation is vital for defending the body from infections, injuries and toxins. However, in Parkinson’s there is excessive chronic inflammation within the brain. It is now believed that this may play a role in the damage to brain cells which occurs in the condition. Previous work carried out by Parkinson’s UK led to the identification of novel small molecules which target a protein found on the surface of microglia, the main immune cells in the brain that become overactive in Parkinson’s. Domainex is conducting an integrated drug discovery programme in order to optimise the pharmaceutical properties within this chemical series with the ultimate aim of nominating a clinical candidate. The goal is to develop a therapy with the potential to slow or stop the progression of Parkinson’s, something no current medication can do.

“Domainex was selected following an extensive review process on the basis of their experience and capability to execute a fully integrated drug discovery project, including the development of neuroinflammation assays and the optimisation of our compounds’ target engagement in the brain.

Dr Richard Morphy, Drug Discovery Manager at Parkinson’s UK

To read the full press release click here.

If you would like to access Domainex’s expertise in CNS drug discovery to support your own research programmes we would be delighted to hear from you.


  1. CNS drug design: balancing physicochemical properties for optimal brain exposure. Zoran Rankovic; Journal of Medicinal Chemistry; 2015;58(6):2584-608. 
  2. CNS Physicochemical Property Space Shaped by a Diverse Set of Molecules with Experimentally Determined Exposure in the Mouse Brain. Zoran Rankovic; Journal of Medicinal Chemistry; 2017, 60, 14, 5943-5954.

Domainex press releases in the field of CNS disorders:

Parkinson’s UK and Domainex collaborate to develop therapies targeting neuroinflammation to slow the progression of Parkinson’s

NRG Therapeutics Selects Domainex to be its Integrated Drug Discovery Partner for its Biomedical Catalyst Funded Parkinson’s Disease Project 


Integrated Drug Discovery for CNS Targets