BIOLOGIC AGENTS AND SMALL MOLECULES – MECHANISM OF ACTION

2022 ◽  
pp. 100861
Author(s):  
Katherine Falloon ◽  
Ruthvik Padival ◽  
Satya Kurada ◽  
Sara El Ouali ◽  
Florian Rieder
Keyword(s):  
Small Molecules ◽  
Mechanism Of Action ◽  
Biologic Agents

scholarly journals Techniques to Study Inflammasome Activation and Inhibition by Small Molecules

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1704
Author(s):  
Diego Angosto-Bazarra ◽  
Cristina Molina-López ◽  
Alejandro Peñín-Franch ◽  
Laura Hurtado-Navarro ◽  
Pablo Pelegrín
Keyword(s):  
Inflammatory Response ◽  
Small Molecules ◽  
Mechanism Of Action ◽  
Inflammatory Diseases ◽  
Inflammasome Activation ◽  
Chronic Inflammatory Diseases ◽  
Anti Inflammatory ◽  
Inhibitory Molecules ◽  
Inflammasome Inhibitors

Inflammasomes are immune cytosolic oligomers involved in the initiation and progression of multiple pathologies and diseases. The tight regulation of these immune sensors is necessary to control an optimal inflammatory response and recover organism homeostasis. Prolonged activation of inflammasomes result in the development of chronic inflammatory diseases, and the use of small drug-like inhibitory molecules are emerging as promising anti-inflammatory therapies. Different aspects have to be taken in consideration when designing inflammasome inhibitors. This review summarizes the different techniques that can be used to study the mechanism of action of potential inflammasome inhibitory molecules.

scholarly journals Ru(II)-Dppz Derivatives and Their Interactions with DNA: Thirty Years and Counting

2021 ◽  
Vol 11 (7) ◽  
pp. 3038
Author(s):  
Maria Letizia Di Pietro ◽  
Giuseppina La Ganga ◽  
Francesco Nastasi ◽  
Fausto Puntoriero
Keyword(s):  
Transition Metal ◽  
Metal Complexes ◽  
Small Molecules ◽  
Transition Metal Complexes ◽  
Mechanism Of Action ◽  
Spectroscopic Techniques ◽  
Biological Applications ◽  
Ancillary Ligands ◽  
Structural Modifications ◽  
Over Time

Transition metal complexes with dppz-type ligands (dppz = dipyrido[3,2-a:2′,3′-c]phenazine) are extensively studied and attract a considerable amount of attention, becoming, from the very beginning and increasingly over time, a powerful tool for investigating the structure of the DNA helix. In particular, [Ru(bpy)2(dppz)]2+ and [Ru(phen)2(dppz)]2+ and their derivatives were extensively investigated as DNA light-switches. The purpose of this mini-review, which is not and could not be exhaustive, was to first introduce DNA and its importance at a biological level and research in the field of small molecules that are capable of interacting with it, in all its forms. A brief overview is given of the results obtained on the Ru-dppz complexes that bind to DNA. The mechanism of the light-switch active in this type of species is also briefly introduced along with its effects on structural modifications on both the dppz ligand and the ancillary ligands. Finally, a brief mention is made of biological applications and the developments obtained due to new spectroscopic techniques, both for understanding the mechanism of action and for cellular imaging applications.

scholarly journals Biochemical investigations of the mechanism of action of small molecules ZL006 and IC87201 as potential inhibitors of the nNOS-PDZ/PSD-95-PDZ interactions

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Anders Bach ◽  
Søren W. Pedersen ◽  
Liam A. Dorr ◽  
Gary Vallon ◽  
Isabelle Ripoche ◽  
...  
Keyword(s):  
Small Molecules ◽  
Mechanism Of Action ◽  
Potential Inhibitors

The situation of small molecules targeting key proteins to combat SARS-CoV-2: Synthesis, metabolic pathway, mechanism of action, and potential therapeutic applications

2021 ◽  
Vol 21 ◽  
Author(s):  
Farzaneh Sorouri ◽  
Zahra Emamgholipour ◽  
Maryam Keykhaee ◽  
Alireza Najafi ◽  
Loghman Firoozpour ◽  
...  
Keyword(s):  
Small Molecules ◽  
Mechanism Of Action ◽  
Metabolic Pathway ◽  
Chemical Structure ◽  
Pediatric Patients ◽  
New Drugs ◽  
Protein Targets ◽  
Global Epidemic ◽  
Therapeutic Applications ◽  
Stimulation Of

: Due to the global epidemic and high mortality of 2019 coronavirus disease (COVID-19), there is an immediate need to discover drugs that can help before a vaccine becomes available. Given that the process of producing new drugs is so long, the strategy of repurposing existing drugs is one of the promising options for the urgent treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease. Although FDA has approved Remdesivir for the use in hospitalized adults and pediatric patients suffering from COVID-19, no fully effective and reliable drug has been yet identified worldwide to treat COVID-19 specifically. Thus, scientists are still trying to find antivirals specific to COVID-19. This work reviews the chemical structure, metabolic pathway, mechanism of action of existing drugs with potential therapeutic applications for COVID-19. Further, we summarized the molecular docking stimulation of the medications related to key protein targets. These already drugs could be developed for further clinical trials to supply suitable therapeutic options for patients suffering from COVID-19.

scholarly journals Inhibition Profiling of Human Carbonic Anhydrase II by High-Throughput Screening of Structurally Diverse, Biologically Active Compounds

2006 ◽  
Vol 11 (7) ◽  
pp. 782-791 ◽  
Author(s):  
Rema Iyer ◽  
Albert A. Barrese ◽  
Shilpa Parakh ◽  
Christian N. Parker ◽  
Brian C. Tripp
Keyword(s):  
Carbonic Anhydrase ◽  
Small Molecules ◽  
Tannic Acid ◽  
High Throughput ◽  
Mechanism Of Action ◽  
High Throughput Screening ◽  
Biologically Active ◽  
Carbonic Anhydrase Ii ◽  
Hit Rate ◽  
Human Carbonic Anhydrase

Human carbonic anhydrase II (CA II), a zinc metalloenzyme, was screened against 960 structurally diverse, biologically active small molecules. The assay monitored CA II esterase activity against the substrate 4-nitrophenyl acetate in a format allowing high-throughput screening. The assay proved to be robust and reproducible with a hit rate of ∼2%. Potential hits were further characterized by determining their IC50 and Kd values and tested for nonspecific, promiscuous inhibition. Three known sulfonamide CA inhibitors were identified: acetazolamide, methazolamide, and celecoxib. Other hits were also found, including diuretics and antibiotics not previously identified as CA inhibitors, for example, furosemide and halazone. These results confirm that many sulfonamide drugs have CA inhibitory properties but also that not all sulfonamides are CA inhibitors. Thus many, but not all, sulfonamide drugs appear to interact with CA II and may target other CA isozymes. The screen also yielded several novel classes of nonsulfonamide inhibitors, including merbromin, thioxolone, and tannic acid. Although these compounds may function by some nonspecific mechanism (merbromin and tannic acid), at least 1 (thioxolone) appears to represent a genuine CA inhibitor. Thus, this study yielded a number of potentially new classes of CA inhibitors and preliminary experiments to characterize their mechanism of action.

scholarly journals If the treatment works, do we need to know why?: the promise of immunotherapy for experimental medicine

2007 ◽  
Vol 204 (10) ◽  
pp. 2249-2252 ◽  
Author(s):  
Michael R. Ehrenstein ◽  
Claudia Mauri
Keyword(s):  
Autoimmune Disease ◽  
Mechanism Of Action ◽  
Biologic Agents ◽  
Biologic Agent ◽  
Experimental Medicine ◽  
Disease Mechanisms

There has been much fanfare, and rightly so, heralding a revolution in the treatment of autoimmune disease using biologic agents—antibodies or other molecules that specifically target known mediators of disease. But not all patients respond to even the most successful biologic agent, which may provide clues about alternate disease mechanisms. Studies aimed at understanding the mechanism of action of biologic agents will yield significant benefits for experimental medicine.

scholarly journals THE SAFETY, TOLERABILITY, AND EFFECTIVENESS OF BIOLOGICS/SMALL MOLECULE THERAPY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND CIRRHOSIS

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S45-S46
Author(s):  
Muyi Li ◽  
Sameer Khan ◽  
Deborah Proctor ◽  
Jill Gaidos ◽  
Badr Al-Bawardy
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Small Molecules ◽  
Small Molecule ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Infusion Reaction ◽  
Mucosal Healing ◽  
Biologic Agents ◽  
Inflammatory Bowel

Abstract Introduction Biologic agents and small molecules have been shown to be effective and relatively safe in the treatment of inflammatory bowel disease (IBD). However, data is lacking regarding the use of these agents in patients with IBD and concomitant cirrhosis. The aim of this study is to examine the safety, tolerability and effectiveness of biologics and small molecules in patients with IBD and concomitant cirrhosis. Methods This is a retrospective study of adult patients diagnosed with both IBD and cirrhosis (by liver biopsy or Fibroscan) treated with biologic agents or small molecule agents between 2012 and 2020 within the Yale-New Haven Hospital system. We included patients on tofacitinib or any of the following biologic agents: infliximab, adalimumab, certolizumab pegol, golimumab, vedolizumab, ustekinumab. Primary outcomes were rates of adverse events (infection, infusion reaction, IBD-related hospitalization) and mortality. Secondary outcomes were clinical remission (defined by the physician global assessment) and mucosal healing (Mayo endoscopic score of 0 or 1 for ulcerative colitis (UC) and absence of erosion/ulcerations in Crohn’s disease (CD)). Results A total of 18 patients (72% CD, 28% UC) with median age of 50 (26–73) years were included (Table 1). Decompensated cirrhosis was present in 33.3% of the population prior to initiation of biologic/small molecule therapy. The most common etiology of cirrhosis was primary sclerosing cholangitis at 38.9%. IBD therapy included: infliximab/adalimumab (44.5%), vedolizumab (27.7%), and ustekinumab (22.2%) and tofacitinib (5.6%). A total of 4 patients (22.2%) were on concomitant corticosteroid therapy and 3 on combination therapy with thiopurines (Table 2). Adverse events occurred in 27.7% (n=5; 1 infusion reaction and 4 infections). The 4 patients with infections included: 2 on infliximab/adalimumab, 1 on ustekinumab, 1 on vedolizumab. Two of these patients were on concomitant thiopurines and 1 on corticosteroid. Biologic therapy was stopped in 3 patients, 2 for non-response and 1 for an infusion reaction. Mortality rate was 11% and all were liver-related. Clinical remission was achieved in 66.7% and mucosal healing was noted in 72.7% (8/11). Conclusions In this cohort of patients with IBD and cirrhosis, biologic/small molecule therapies were effective for IBD. Approximately a quarter of patients experienced adverse events that were mainly due to infections. Larger studies are needed to elucidate the relative safety of different biologic agents and small molecules in IBD patients with cirrhosis.

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