A5046028117- COVID-19 Clinical Research Studies
- Synthesis and biological activity
- SARS-CoV-2 and COVID-19 Research
- Influenza Virus Research Studies
- interferon and immune responses
- Click Chemistry and Applications
- Synthesis and Biological Evaluation
- Hepatitis C virus research
- Genomics, phytochemicals, and oxidative stress
- Computational Drug Discovery Methods
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- HIV/AIDS drug development and treatment
- PARP inhibition in cancer therapy
- Synthesis and Characterization of Heterocyclic Compounds
- Long-Term Effects of COVID-19
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- Multicomponent Synthesis of Heterocycles
- RNA and protein synthesis mechanisms
- Cancer therapeutics and mechanisms
- NF-κB Signaling Pathways
- COVID-19 diagnosis using AI
- Acute Myeloid Leukemia Research
- Estrogen and related hormone effects
ChemDiv (United States)
2022-2024
Chemical Diversity Research Institute
2007-2020
Lomonosov Moscow State University
2000-2005
In May 2020 the Russian Ministry of Health granted fast-track marketing authorization to RNA polymerase inhibitor AVIFAVIR (favipiravir) for treatment COVID-19 patients. pilot stage Phase II/III clinical trial, enabled SARS-CoV-2 viral clearance in 62.5% patients within 4 days, and was safe well-tolerated. Clinical Trials Registration. NCT04434248.
Animal cells counteract oxidative stress and electrophilic attack through coordinated expression of a set detoxifying antioxidant enzyme genes mediated by transcription factor Nrf2.In unstressed cells, Nrf2 appears to be sequestered in the cytoplasm via association with an inhibitor protein, Keap1.Here, using yeast two-hybrid screen, human Keap1 has been identified as partner nuclear protein prothymosin ␣.The vivo vitro data indicated that ␣-Keap1 interaction is direct, highly specific,...
// Elena I. Fedoros 1, 5 , Alexey A. Orlov 2 Alexander Zherebker 2, 8 Ekaterina Gubareva 1 Mikhail Maydin Andrey Konstantinov Konstantin Krasnov 3 Ruben N. Karapetian 4 Izotova Sergey E. Pigarev V. Panchenko Margarita L. Tyndyk Dmitry Osolodkin 6, 7 Evgeny Nikolaev 8, 9, 10 Irina Perminova and Vladimir Anisimov N.N. Petrov National Medical Research Center of Oncology, Saint-Petersburg 197758, Russia Department Chemistry, Lomonosov Moscow State University, 119991, Institute Toxicology,...
4-Substituted 2,4-dioxobutanoic acids inhibit influenza virus cap-dependent endonuclease (CEN) activity. Baloxavir marboxil, 4, is approved for treating infections. We describe here the synthesis and biological evaluation of active compounds, 5a–5g, their precursors (6a, 6b, 6d, 6e) with flexible bulky hydrophobic groups instead rigid polyheterocyclic moieties. In silico docking confirmed ability 5a–5g to bind site A CEN (PDB code: 6FS6) like baloxavir acid, 3. These novel compounds...
ABSTRACT In May 2020 the Russian Ministry of Health granted fast-track marketing authorization to RNA polymerase inhibitor AVIFAVIR (favipiravir) for treatment COVID-19 patients. pilot stage Phase II/III clinical trial, enabled SARS-CoV-2 viral clearance in 62.5% patients within 4 days, and was safe well-tolerated.
A new chemical series was identified via high-throughput screening as having antiproliferative activity on DU-145 human prostate carcinoma cell line (hit compound potency - 2.9 microM). Medicinal chemistry optimization of two peripheral diversity vectors the hit molecule, independently, led to SAR generalizations and identification 'best' moieties. The latter were merged in a single that exhibited an over 100-fold better than compound. For most potent compounds it confirmed observed not...
ObjectivesDevelopment of a novel drug candidate with improved potency against influenza virus neuraminidase compared currently available therapeutics, and high activity oseltamivir-resistant viruses.
A series of next in class small-molecule hepatitis C virus (HCV) NS5A inhibitors with picomolar potency containing 2-pyrrolidin-2-yl-5-{4-[4-(2-pyrrolidin-2-yl-1H-imidazol-5-yl)buta-1,3-diynyl]phenyl}-1H-imidazole cores was designed based on the SAR studies available for reported inhibitors. Compound 13a (AV4025), (S,S,S,S)-stereochemistry (EC50 = 3.4 ± 0.2 pM, HCV replicon genotype 1b), dramatically more active than were compounds two (S)- and (R)-chiral centers. Human serum did not...
Based on the structure of previously identified leads, new series compounds containing 1,2,4-oxadiazole core was designed. A small, diverse library 51 including both 2-(acylamino)ethyl and 2-ureidoethyl side chains synthesized using parallel chemistry tested for antiproliferative activity against prostate cancer DU-145 cell line. Four hit – all belonging to were three confirmed as 10-20 µM inhibitors. The similarity in compounds’ periphery data obtained suggest a similar mode action these...
Abstract Background The development and clinical implementation of the cap-dependent endonuclease (CEN) inhibitor baloxavir marboxil was a breakthrough in influenza therapy, but it associated with emergence drug-resistant variants. Objectives To design synthesize structural analogues CEN inhibitors evaluate their safety, pharmacokinetics antiviral potency vitro vivo. Methods drug candidate AV5124 its active metabolite AV5116 were synthesized based on pharmacophore modelling. Stability plasma...
COVID-19 is a contagious multisystem inflammatory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We studied the efficacy of Aprotinin (nonspecific serine proteases inhibitor) in combination with Avifavir® or Hydroxychloroquine (HCQ) drugs, which are recommended Russian Ministry Health for treatment therapy moderate patients. This prospective single-center study included participants COVID-19-related pneumonia, laboratory-confirmed SARS-CoV-2, and admitted to...
A new chemical series of antiproliferative compounds was identified via high-throughput screening on DU-145 human prostate carcinoma cell line (hit compound potency - 5.7 microM). Exploration the two peripheral diversity vectors hit molecule in a hit-targeted library and testing resulting led to SAR generalizations identification 'best' pharmacophoric moieties. The latter were merged single that exhibited 200-fold better than original compound. Specific cancer cytotoxicity confirmed for most...
This article is to highlight the chemical properties and primary pharmacology of novel GPR119 agonist ZB-16 its analogs, which were rejected during screening. Experiments performed in vitro (specific activity, metabolism cell toxicity) vivo (hypoglycemic activity pharmacokinetics). exhibits nanomolar (EC50 = 7.3-9.7 nM) on target receptor associated with hypoglycemic vivo. In animals streptozotocin-nicotinamide induced type 2 diabetes mellitus (STZ-NA T2D) daily oral dose (1 mg/kg) or...
The divalent cation binding properties of human prothymosin α, an abundant nuclear protein involved in cell proliferation, were evaluated. By using α retardation on a weak chelating resin charged with various cations, specific Zn 2+ ions by was observed. This finding further confirmed the equilibrium dialysis analysis which demonstrated that, within micromolar range concentrations, could bind up to three zinc presence 100 m NaCl and 13 absence NaCl. Equilibrium also revealed that Ca ,...
Recently new drugs targeting androgen-dependent axis have been approved for the treatment of castration-resistant prostate cancer (CRPC) - Zytiga and Xtandi (formerly MDV3100), several other candidates (for example, ARN-509) are in early phases clinical trials. However despite significant improvement overall survival with treatments it is evident that resistance to these develops. One approaches overcome combination therapy from this point view some potential drug-drug interactions can limit...
Neuraminidase inhibitors (NAIs) are recommended for influenza treatment and prevention worldwide. The most widely prescribed NAI is oral oseltamivir, while inhaled zanamivir less commonly used. Using phenotypic neuraminidase (NA) enzymatic assays molecular modeling approaches, we examined the ability of investigational orally-dosed AV5080 to inhibit viruses A(H1N1)pdm09, A(H3N2), A(H5N1), A(H7N9) subtypes B/Victoria- B/Yamagata-lineages containing NA substitutions conferring oseltamivir or...
The efficacy of Aprotinin as prophylactic treatment Covid-19 was studied in the hamster model SARS-CoV-2 and health care personnel working with patients hospital. High pre- post-exposure prophylaxis demonstrated.
Aprotinin showed high efficacy and safety in a prospective study of combination therapy for hospitalized patients with moderate to severe COVID-19 pneumonia.
The efficacy of aprotinin combinations with selected antiviral-drugs treatment influenza virus and coronavirus (SARS-CoV-2) infection was studied in mice models pneumonia COVID-19. high the reducing titer lungs body weight loss increasing survival rate were demonstrated. This preclinical study can be considered a confirmatory step before introducing into clinical assessment.