A5068551337- Studies on Chitinases and Chitosanases
- Invertebrate Immune Response Mechanisms
- Parasites and Host Interactions
- Cytokine Signaling Pathways and Interactions
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Peptidase Inhibition and Analysis
- Chronic Myeloid Leukemia Treatments
- Insect symbiosis and bacterial influences
- Nematode management and characterization studies
- Lymphoma Diagnosis and Treatment
- Trypanosoma species research and implications
- Chronic Lymphocytic Leukemia Research
- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Galectins and Cancer Biology
- Cancer-related Molecular Pathways
- Fibroblast Growth Factor Research
- Heat shock proteins research
- Kruppel-like factors research
- Antimicrobial Peptides and Activities
- Protein Hydrolysis and Bioactive Peptides
- Genetics, Aging, and Longevity in Model Organisms
- X-ray Diffraction in Crystallography
- Melanoma and MAPK Pathways
CURE International UK
2024
OncoArendi Therapeutics (Poland)
2017-2022
Celon Pharma (Poland)
2012-2022
Medical University of Warsaw
2022
Postgraduate School of Molecular Medicine
2022
Queen's University
2012
Accumulation of molecular damage and increased heterogeneity are hallmarks cellular aging. Mild stress-induced hormesis can be an effective way for reducing the accumulation damage, thus slowing down aging from within. We have shown that repeated mild heat stress (RMHS) has anti-aging effects on growth various other biochemical characteristics normal human skin fibroblasts keratinocytes undergoing in vitro. RMHS given to cells basal levels chaperones, reduced damaged proteins, stimulated...
Up to 10 % of primary gastric cancers are characterized by FGFR2 amplification, and fibroblast growth factor receptor (FGFR) inhibitors may represent therapeutic agents for patients with these malignancies. However, long-term benefits the treatment might be limited owing occurrence drug resistance. To investigate mechanisms resistance selective FGFR inhibitors, we established three FGFR2-amplified SNU-16 cancer cell lines resistant AZD4547, BGJ398, PD173074, respectively. The (SNU-16R)...
We designed and synthesized a series of arginase inhibitors as derivatives the well-known 2-(S)-amino-6-boronohexanoic acid (ABH) with basic neutral side chains in α-position relative to amino group. In an effort improve pharmacokinetic profile literature examples retain potent enzymatic activity, sulfamido moieties were introduced generate hydrogen bond interaction aspartic residue active site. The compounds guanidine-containing even more inhibitors. Both groups compounds, designed,...
Idiopathic pulmonary fibrosis (IPF) is a progressive and eventually fatal lung disease with complex etiology. Approved drugs, nintedanib pirfenidone, modify progression, but IPF remains incurable there an urgent need for new therapies. We identified chitotriosidase (CHIT1) as driver of in novel therapeutic target. demonstrate that CHIT1 activity expression are significantly increased serum (3-fold) induced sputum (4-fold) from patients. In the lungs expressed distinct subpopulation...
Crizotinib, the first FDA-approved ALK inhibitor, showed significant antitumor activity in young patients with anaplastic large-cell lymphoma (ALCL) frequently displaying rearrangement. However, long-term therapeutic benefits of crizotinib are limited due to development drug resistance. CH5424802--more potent and selective inhibitor--comprises a good candidate for second-line treatment crizotinib-relapsed patients. The aim this study was determine possible mechanisms resistance inhibitors...
Chitotriosidase (CHIT1) is an enzyme produced by macrophages that regulates their differentiation and polarization. Lung have been implicated in asthma development; therefore, we asked whether pharmacological inhibition of macrophage-specific CHIT1 would beneficial effects asthma, as it has shown previously other lung disorders. expression was evaluated the tissues deceased individuals with severe, uncontrolled, steroid-naïve asthma. OATD-01, a chitinase inhibitor, tested 7-week-long house...
This article highlights our work toward the identification of a potent, selective, and efficacious acidic mammalian chitinase (AMCase) inhibitor. Rational design, guided by X-ray analysis several inhibitors bound to human chitotriosidase (hCHIT1), led compound 7f as highly potent AMCase inhibitor (IC50 values 14 19 nM against mouse enzyme, respectively) selective (>150× mCHIT1) with very good PK properties. dosed once daily at 30 mg/kg po showed significant anti-inflammatory efficacy in...
Acidic mammalian chitinase (AMCase) and chitotriosidase-1 (CHIT1) are two enzymatically active proteins produced by mammals capable of cleaving the glycosidic bond in chitin. Based on clinical findings animal model studies, involvement chitinases has been suggested several respiratory system diseases including asthma, COPD, idiopathic pulmonary fibrosis. Exploration structure–activity relationships within series 1-(3-amino-1H-1,2,4-triazol-5-yl)-piperidin-4-amines, which was earlier...
Chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) are the enzymatically active chitinases that have been implicated in pathology of chronic lung diseases such as asthma interstitial (ILDs), including idiopathic pulmonary fibrosis (IPF) sarcoidosis. The clinical preclinical data suggest pharmacological inhibition CHIT1 might represent a novel therapeutic approach IPF. Structural modification an advanced lead molecule 3 led to identification compound 9 (OATD-01), highly inhibitor...
Sarcoidosis is a systemic disease of unknown etiology characterized by granuloma formation in the affected tissues. The pathologically activated macrophages are causatively implicated pathogenesis and play important role formation. Chitotriosidase (CHIT1), macrophage-derived protein, upregulated sarcoidosis its levels correlate with severity implicating CHIT1 pathology.CHIT1 was evaluated serum bronchial mucosa mediastinal lymph nodes specimens from patients. therapeutic efficacy OATD-01...
Human acidic mammalian chitinase (hAMCase) is one of two true chitinases in humans, the function which remains elusive. In addition to defense against highly antigenic chitin and chitin-containing pathogens gastric intestinal contents, AMCase has been implicated asthma, allergic inflammation, ocular pathologies. Potent selective small-molecule inhibitors this enzyme have not identified date. Here we describe structural modifications compound OAT-177, a previously developed inhibitor mouse...
<b>Rationale:</b> Chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) are the enzymatically active chitinases in humans. CHIT1 has been implicated pathogenesis of interstitial lung diseases (ILDs) including IPF. <b>Methods:</b> Chitinolytic activity was assessed induced sputum (IS) serum from IPF patients controls (n=20-28) expression evaluated bronchoalveolar lavage (BAL) cells patients. The therapeutic efficacy OATD-01 – a selective inhibitor mouse model bleomycin-induced...
Chitinases and chitinase-like proteins are thought to play a role in innate inflammatory responses. Our study aimed assess whether chitinase concentration activity induced sputum (IS) of patients exposed tobacco smoke related the level airway inflammation including chitinases proteins. The included 22 with chronic obstructive pulmonary disease (COPD), 12 non-COPD smokers, nine nonsmoking subjects. Sputum CHIT1 YKL-40 levels chitinolytic were compared IL-6, IL-8, IL-18, MMP-9 levels. A...
TRAF-2 and NCK-interacting kinase (TNIK) is a serine–threonine with proposed role in Wnt/β-catenin JNK pathways.
Phosphoinositide 3-kinase δ (PI3Kδ), a member of the class I PI3K family, is an essential signaling biomolecule that regulates differentiation, proliferation, migration, and survival immune cells. The overactivity this protein causes cellular dysfunctions in many human disorders, for example, inflammatory autoimmune diseases, including asthma or chronic obstructive pulmonary disease (COPD). In work, we designed synthesized new library small-molecule inhibitors based on...
Abstract OATD-01 is a chitinase-1 (CHIT1) inhibitor, reducing inflammation and fibrosis in animal models where chronic leads to tissue remodeling. CHIT1, predominantly secreted by macrophages, overexpressed metabolic-dysfunction-associated steatohepatitis (MASH). In this study, we demonstrated the efficacy of two murine rat model MASH. RNA-Seq analysis revealed that reversed MASH-dysregulated genes. Apart from attenuation fibrosis, regulated metabolic processes such as lipid metabolism...
<b>Introduction:</b> OATD-01 is a small molecule inhibitor of acidic mammalian chitinase (AMCase) and chitotriosidase (CHIT1), that developed as an oral treatment for respiratory diseases. The efficacy was demonstrated in number vivo models asthma pulmonary fibrosis. <b>Objectives:</b> Assessment safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) metabolism were the main objectives this first-in-human, single ascending dose study healthy male volunteers. <b>Methods:</b> 48...
<b>Introduction:</b> Acidic mammalian chitinase (AMCase) and chitotriosidase (CHIT1) are enzymatically active chitinases implicated in pathology of respiratory disorders such as asthma COPD. <b>Objectives:</b> The aim the study was to evaluate therapeutic efficacy OAT-889, a novel dual AMCase/CHIT1 inhibitor chronic airway inflammation model compare it with montelukast, an oral leukotriene receptor antagonist used maintenance therapy asthma. <b>Methods:</b> mice induced by 7-week-long...