Target Medicals is focused on research of clinically relevant Cytochrome P450s – а special enzymes, playing a crucial role in bioregulation processes in human and microorganisms.

Cytochrome P450s (CYPs) are a major source of variability in drug pharmacokinetics and response. Of 57 putatively functional human CYPs only about a dozen enzymes, belonging to the CYP 1, 2, and 3 families, are responsible for the biotransformation of most foreign substances, including 70–80% of all drugs in clinical use. Expression of each CYP is influenced by a unique combination of mechanisms and factors including genetic polymorphisms, induction by xenobiotics, regulation by cytokines, hormones and during disease states, as well as sex, age and others.


Based on our scientific achievements we have developed a unique technological platform — CRISTA — designed for P450-targeted drug discovery, based on integration of scientific achievement in structural biology and molecular endocrinology as well as the use of bioinformatics, experimental and technological practices of synthesis the compounds with desired properties.

protein crystallization

Crystallography remains one of the most multidisciplinary sciences that links together frontier areas of research and has, directly or indirectly, produced the largest number of Nobel Laureates throughout history.

Our unique achievements in proteins crystallization allow us to discover the most specific compounds to bind/inhibit a certain target. In our portfolio we have 15 crystal structures of CYPs.

development of high-throughput screening of drug candidates

Cytochrome P450s possess unique spectral property – transition of a heme iron from low-spin to a high-spin state upon ligand binding to the active site. It is accompanied by a shift in absorbance peak from 417 nm to 393 nm (Sore region). We utilize this feature in high-throughput screening of inhibitors using the Laboratory Automation Microdispenser Workstation and microplate UV-VIS readers.

nmr-based methods in hit-to-lead optimization

P450 cytochrome has a paramagnetic center – iron. Therefore, from nuclear magnetic resonances spectra it is possible to calculate the distance from the paramagnetic center (iron of heme) to the protons of the ligand that bound at the active center of cytochrome P450. The combination of information on crystal structure and on relative positions of individual atoms of ligand, along with ligand-protein kinetic parameters will allow design and further testing of Hit compounds with increased specificity and binding affinity.

high-performance in silico screening 

Virtual screening in silico is a commonly used method for drug-design. The binding mode prediction and interaction energy of small molecules with the binding pocket will be calculated in Program suite Amber 12. Commercial databases will be used for compounds screening. The best hits will be checked in vitro assays. It should be noted that docking software is optimized for speed of execution, but not for the prediction of binding energy, so there are more accurate methods for the determination of the thermodynamic parameters of the interaction. Such methods as thermodynamic integration and free energy perturbation will be used for modeling. In order to reproduce the real behavior of molecules in dynamics, energy parameters will be calculated on the basis of experimental data (for example, spectroscopic) and quantum mechanical calculations. This parametrization is named force field and will include parameters for rigidity, length of harmonic “springs”, which describe bond length and valence angles and also parameters of electrostatic, dispersion and exchange-correlation interactions. Classical methods, which are based on molecular dynamics, will be used for investigation of proteinligand interaction.

analytical methods

Quantitative estimation of interaction parameters of P450 with ligands and catalytic activity requires a precise determination of enzymes concentration.

determination of enzymatic activity

After the identification of the active site ligands it is necessary to analyze their inhibitory effect on the enzymatic activity of the target.