CEPHARES
Research Program
The concept of the program and scope of research, which will be performed in CEPHARES, respond to one of the greatest current and foreseeable societal challenges that is central nervous system (CNS) disorders, in particular threats to human mental health. The strategy adopted in the Center is focused on integration of actions around the creation of a scientific basis for placement of ground-breaking medicines targeting the CNS on the market. Technologically advanced laboratories will be used to carry out a comprehensive program of studies from the design of the molecule to the fully validated substance with the potential to become a drug and meeting requirements for permission to conduct clinical trials.
The complete CNS drug candidate development program will be implemented using ultramodern methods: chemo- and bioinformatics, medical chemistry, organic synthesis, analytics, biochemistry, molecular biology, electrophysiology, transgenics and a wide spectrum of purely pharmacological methods with the use of animal models of CNS diseases.
BASIC RESEARCH
Considering the existing and still growing threats posed by CNS disorders and experience of IP PAS in this field,the research strategy accepted for the next several years will be oriented first of all towards diseases considered to be diseases of civilization, including mental disorders (depression, psychotic disorders) and anxiety disorders (phobias, post-traumatic stress disorder), neurodegenerative diseases (Parkinson’s disease, Alzheimer’s disease) and psychactive substance use disorders, including addiction to designer drugs.
The above-mentioned categories of diseases are priority research areas in the upcoming years, however, studies on other therapeutic targets linked with CNS disorders, such as psychosomatic pain treatment strategies, are not excluded. Basic research within the above-defined thematic scopes carried out in order to broaden our knowledge and to understand the neurobiological bases of neurochemical disturbances will focus on:
development of molecular probes as highly specific tool compounds and their use to study disarrayed neurotransmission
development of early diagnostic techniques by searching for biomarkers and neurochemical and neurobiological basis of pathological changes
The spotlight will be on searching for molecules and analysis of their interaction with different types of central receptors: glutamatergic, monoaminergic, cannbinoidergic and GABAergic GPCRs, and selected ion channels, adopting the latest concepts in pharmacology, i.e. allosteric modulation, functional selectivity and capacity of homo- and hetero-oligomerization.
Drug discovery
The studies at the stage of searching for compounds with the desired biological activity will focus on:
therapeutic target identification and validation, and molecular studies on the pathogenetic
design of new compounds with the required biological activity in the CNS
synthesis and optimization of active compounds (hit to lead)
high throughput screening n(HTS) to confirm lead compound activity at the therapeutic targets using in vitro methods
Preclinical development
Preclinical development of drug candidates includes:
thorough in vitro characterization of lead compounds in terms of CNS receptor interaction profile (G protein-coupled receptors and ion channels), definition of target and off-target activity, and determination of basic toxicity (cell proliferation, viability, apoptosis and necrosis) (2D and 3D)
deteremination of ADMET/PK parameters
studies of the mechanism of action of new CNS ligands based on advanced ex vivo biochemical, electrophysiological and moledcular imaging methods, and quantitative and spatial distribution studies in brain structures
in vivo characteristics of lead componds selected as candidates for clinical trials in targeted CNS diseases
CEPHARES’ STRUCTURE
CEPHARES is a separate research space, which in terms of technical requirements is tailored to every stage of new drug development, in accordance with ergonomics principles of Drug Discovery and Development process, and to providing advanced research services to the Life Science sector. Every CEPHARES module CF1 – CF5 will be equipped with state-of-the-art, highly automated research instrumentation for drug chemistry, bioinformatics, imaging, molecular biology, electrophysiological transgenics studies and pharmacological tests in behavioral models of CNS diseases. In addition, after reconstruction and modernization, the buildings at 52 Ojcowska Street in Kraków will house the Science Information Center created as the CF6 module of CEPHARES, which will be engaged in gathering, digitalization, archiving and publicizing of the results of research carried out in CEPHARES.
Module CF6 will comprise: Conference and Training Venue performing tasks related to organization of meetings and training seminars, Entrepreneureship Platform involved in providing laboratory infrastructure to spin-off companies and external research groups who wish to conduct their own innovative projects, and the Reference Center of Leica, the world leader in micro- and nano-imaging, created with the support of KAWA.SKA company and allowing a wide access to the latest technological solutions.
Laboratories and research units will operate within the framework of 6 modules CF1 – CF6.
