The Molecular Pharmacology Laboratory was established through a subsidy from the federal budget of the Russian Federation for the purpose of providing state support for scientific research conducted under the guidance of leading scientists in Russian higher professional education institutions via a Government of the Russian Federation grant for research in the field of "Proteomics. Molecular Pharmacology. Medicinal Chemistry."
The project aim is to continue research into the physiological function of p53 family proteins (p63, p73) and to study the mechanisms regulating their stability through small inhibitors of the E3-specific ubiquitin ligase ITCH.
Main project objectives
- Study the effect of p73-specific ITCH ubiquitin ligase inhibitors on the stability of the latter.
- Create a new, more specific library of molecular ITCH inhibitors.
- Verify the tumor-suppressive functions of combined chemotherapy with ITCH inhibition.
- Potential application of ITCH inhibitors in the treatment of neurodegenerative diseases and inflammatory processes.
Planned scientific results
- Obtain a new sample of a synthesized library of compounds (leads) based on the obtained E3 ligase Itch inhibitor
- Obtain a new sample of E3 ligase Itch inhibitor molecules
Tasks addressed
- Search for new pharmacological substances using combinatorial chemistry technologies and high-throughput screening
- Development of new drug substances using original "best-in-class" technology
- Search for new therapeutic indications for drug applications
- Study of the molecular and cellular mechanism of action of drug substances on panels of the latest biotargets
- Search for innovative combinations of drug substances using in vitro & in vivo tests
- Services for in vitro screening of compounds based on high-performance microscopy
- Services for genome-wide gene expression analysis using microarray hybridization
- Proteomic analysis of differentially expressed biotargets using DIGE and iTRAQ technologies
- Enzyme analysis (kinases, proteases, phosphatases, methylases, acetylases)
Experimental approaches
Panel screening of the pharmacological activity of chemical compounds performs one of the main tasks of comprehensive research - identifying activity on various types of biological targets (kinases, proteases, and other types of enzymes, effects on ion channels, membrane receptors). Screening is conducted for both cell models and recombinant proteins, depending on the assay type. Based on the research results, the best compounds are selected and optimized according to various criteria, after which the most effective and least toxic compounds undergo the research procedure again. The screening study allows for a decision on further investigation of the substance in preclinical animal studies, the cost of which can significantly exceed screening and modeling using cell cultures. The equipment of the Molecular Pharmacology laboratory includes a PerkinElmer “Operetta” workstation with multimodal readers for 96/384-well plates, capable of testing more than 25,000 compounds per day, allowing for several simultaneous studies of in vitro biological activity.Based on the results of in vitro screening, a work plan is developed for further study of the compound's specific activity.
The equipment available in the laboratory allows for the prediction of biological targets for existing drugs with unknown molecular mechanisms of action. The biological effect of a compound can be assessed by its impact on changes in gene expression using an Agilent microarray scanner to identify the putative signaling pathway activated by the substance. The drug's effect is also evaluated through gene expression analysis at the protein level. For these purposes, the laboratory is equipped with a BioRad 2D electrophoresis system, a documentation station, and a BioRad spot-cutter robot for the automated excision of differentially expressed protein spots from the gel.
A suite of equipment unique among Russian laboratories enables a full cycle of pharmacological research, from searching for potential targets for new drugs to the preliminary assessment of their pharmacological activity. The laboratory staff includes employees and postgraduate students with backgrounds in molecular biology, molecular genetics, and biophysics. All laboratory staff have experience working in both Russian and Western laboratories. The expertise of the staff allows for the maximum utilization of the available equipment to solve the most complex biological problems.
Website: https://mol-pharm.com
Contact person: Gennaro Melino
Address: 26 Moskovsky Ave.
Phone: +7 (812) 494-92-66
Contact person: Gennaro Melino
Address: 26 Moskovsky Ave.
Phone: +7 (812) 494-92-66
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