A5089223533- Studies on Chitinases and Chitosanases
- Invertebrate Immune Response Mechanisms
- Neuropeptides and Animal Physiology
- Insect symbiosis and bacterial influences
- Receptor Mechanisms and Signaling
- Peptidase Inhibition and Analysis
- Pineapple and bromelain studies
- Chemical Synthesis and Analysis
- Biochemical and Structural Characterization
- Nematode management and characterization studies
- Parasites and Host Interactions
- Gastroesophageal reflux and treatments
- Cancer Research and Treatments
- Gastrointestinal motility and disorders
- Cell death mechanisms and regulation
- Melanoma and MAPK Pathways
- Trypanosoma species research and implications
- Crystallization and Solubility Studies
- Diet, Metabolism, and Disease
- Protein Hydrolysis and Bioactive Peptides
- Antimicrobial Peptides and Activities
- Cancer Mechanisms and Therapy
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cellular Mechanics and Interactions
- X-ray Diffraction in Crystallography
OncoArendi Therapeutics (Poland)
2017-2022
Medical University of Lodz
2021-2022
Santen (Japan)
2014
Aim Overcoming therapy resistance is critical for effective melanoma control. Upregulation of Rho/MRTF signaling in human and mouse melanomas causes to targeted therapies. Inhibition this pathway by MRTFi, CCG-257081 resensitized resistant BRAF MEK inhibitors. It also prevented the development vemurafenib (Vem). Here, we investigate role apoptosis protein pirin CCG-257081-mediated suppression drug resistance. Methods Using naïve YUMMER cells, studied effect inhibitor Vem with or without on...
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...
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...
Chitinase-3-like-1 (CHI3L1), also known as YKL-40, is a glycoprotein linked to inflammation, fibrosis, and cancer. This study explored CHI3L1's interactions with various oligosaccharides using microscale thermophoresis (MST) AlphaScreen (AS). These investigations guided the development of high-throughput screening assays assess interference small molecules in binding between CHI3L1 biotinylated or heparan sulfate-based probes. Small molecule binders YKL-40 were identified our chitotriosidase...
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...
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...
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...
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...
Inflammatory bowel diseases (IBD) are chronic and relapsing gastrointestinal disorders, where a significant proportion of patients unresponsive or lose response to traditional currently used therapies. In the current study, we propose new concept for anti-inflammatory treatment based on selective acidic mammalian chitinase (AMCase) inhibitor. The functions chitinases remain unclear, but they have been shown be implicated in pathology various inflammatory disorders regarding lung (asthma,...
<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...
Irritable bowel syndrome (IBS) is a chronic condition with recurring gastrointestinal (GI) symptoms: altered motility and abdominal pain. As endogenous opioid system participates in pain perception the control of GI peristalsis, opioids have been proposed as promising therapy IBS. In previous study, we observed that morphiceptin derivative, P-317 (Dmt-cyclo-(D-Lys-Phe-D-Pro-Asp)-NH2), presents features to be applied this project, tested whether modifications cyclic morphiceptin-based...
Abstract Aim Overcoming therapy resistance is critical for effective melanoma control. Upregulation of Rho/MRTF signaling in human and mouse melanomas causes to targeted therapies. Inhibition this pathway by MRTFi, CCG-257081 resensitized resistant BRAF MEK inhibitors. It also prevented the development vemurafenib (Vem). Here, we investigate role apoptosis protein pirin CCG-257081-mediated suppression drug resistance. Methods Using naïve YUMMER cells, studied effect inhibitor Vem with or...
<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...