Central nervous system diseases

The blood-brain barrier (BBB) is the complex network of brain microvessels. It protects the brain from the external bloodstream environment and supplies the brain with the required nutrients for normal function. However, blood-brain barrier is also the obstacle to deliver beneficial drugs to treat CNS (central nervous system) diseases or brain tumors, as it has the least permeable capillaries in the entire body due to physical barriers (tight junctions). Therefore, it is crucial to discover drugs which can cross this barrier for the treatment of brain-based diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and epilepsy.

MCE offers a unique collection of 877 compounds with confirmed CNS-Penetrant property. It’s a useful tool for the discovery of drugs used for brain diseases, such as brain tumors, mental disorders, and neurodegenerative diseases.

Neuronal Signaling is involved in the regulation of the mechanisms of the central nervous system (CNS) such as its structure, function, genetics and physiology as well as how this can be applied to understand diseases of the nervous system. Every information processing system in the CNS is composed of neurons and glia, neurons have evolved unique capabilities for intracellular signaling (communication within the cell) and intercellular signaling (communication between cells). G protein-coupled receptors (GPCRs), including 5-HT receptor, histamine receptor, opioid receptor, etc. are the largest class of sensory proteins and are important therapeutic targets in Neuronal Signaling. Besides, Notch signaling, such as β- and γ-secretase, also plays multiple roles in the development of the CNS including regulating neural stem cell (NSC) proliferation, survival, self-renewal and differentiation. GPCR dysfunction caused by receptor mutations and environmental challenges contributes to many neurological diseases. Notch signaling in neurons, glia, and NSCs is also involved in pathological changes that occur in disorders such as stroke, Alzheimer's disease and CNS tumors. Thus, targeting Neuronal Signaling, such as notch signaling and GPCRs, can be used as therapeutic interventions for several different CNS disorders.

MCE designs a unique collection of 2,733 Neuronal Signaling-related compounds that act as a useful tool for the research of neuronal regulation and neuronal diseases.

Exosomes are small membrane vesicles of endocytic origin that are secreted by most cells in culture. Exosomes contain nucleic acids, proteins, lipids, amino acids, and metabolites, etc. Their diverse constituents can reflect their cell of origin. Exosomes are associated with immune responses, viral pathogenicity, pregnancy, cardiovascular diseases, central nervous system-related diseases, and cancer progression. Proteins, metabolites, and nucleic acids delivered by exosomes into recipient cells effectively alter their biological response. Such exosome-mediated responses can be disease promoting or restraining.

The biology of exosomes in disease is still emerging, and the number of studies addressing their utility in the diagnosis and treatment of various pathologies has increased substantially. MCE supplies a unique collection of 46 compounds with the activity of inhibiting or stimulating exsomes secretion/biosynthesis. MCE Exosomes Compound Library is a useful tool for exsomes research.

Neurodegenerative diseases are characterised by progressive dysfunction and death of neurons, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis (MS). Neuroprotection is an approach to preserve neurons so that neurons cannot be hurt by different pathological factors in neurodegenerative diseases. Neuroprotectors are some agonists and antagonists targeting some key targets in neuroprotactive signal pathways, such as calcium and sodium channel blockers, GABA receptor agonists, NMDA receptor Antagonists, etc. Current neuroprotectors cannot reverse existing damage, but they may protect against further nerve damage and slow down any degeneration of the central nervous system (CNS) and still play important roles in the treatment of neurodegenerative diseases.

MCE offers a unique collection of 1,133 compounds with potential neuroprotective activities. These compounds mainly act on some key targets in neuroprotetive signal pathways, such as calcium channel, sodium channel, adenosine A1 receptor, etc. MCE Neuroprotective Compopund Library is a useful tool in neuroprotective drug discovery.

Most of molecules enter or leave cells mainly via membrane transport proteins, which play important roles in several cellular functions, including cell metabolism, ion homeostasis, signal transduction, the recognition process in the immune system, energy transduction, etc. There are three major types of transport proteins, ATP-powered pumps, channel proteins and transporters. Transport proteins such as channels and transporters play important roles in the maintenance of intracellular homeostasis, and mutations in these transport protein genes have been identified in the pathogenesis of a number of hereditary diseases. In the central nervous system, ion channels have been linked to, but not limited to, many diseases such asataxias, paralyses, epilepsies, and deafness. This indicates the roles of ion channels in the initiation and coordination of movement, sensory perception, and encoding and processing of information. Ion channels are a major class of drug targets in drug development.

MCE designs a unique collection of 1,491 smal-molecule modulators that can be used for the research of Ion Channel and Membrane Transporter or high throughput screening (HTS) related drug discovery.

The incidence and significance of central nervous system diseases are increasing at an alarming rate all over the world. Although substantial research efforts have been applied to develop new CNS-active drugs, only a few CNS disorders are addressed satisfactorily, while the remaining ones pose significant clinical challenges. Blood-brain barrier (BBB) permeability is one of the most important limiting factors in the design and development of novel CNS-targeted pharmaceuticals for the treatment of neurological disorders.

Carefully selected from the HTS Compound Collection to meet the parameters optimized for high BBB-permeability, our CNS Focused Screening Library comprising over 30,300 structurally-diverse and potentially CNS-active screening compounds. This original Screening Compound Library is aimed at supporting CNS drug design projects and HTS efforts in search for novel neurotherapeutics.