Review
Biochemistry & Molecular Biology
Martin Alexander Schick, Nicolas Schlegel
Summary: Phosphodiesterase 4 inhibitors play an important role in regulating physiological functions and treating diseases, but they also carry significant risks of serious side effects. This review aims to provide a comprehensive overview of the approaches and effects of phosphodiesterase 4 inhibition in different therapeutic applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Jian Jin, Francesca Mazzacuva, Letizia Crocetti, Maria Paola Giovannoni, Agostino Cilibrizzi
Summary: Cyclic nucleotide phosphodiesterases 4 (PDE4) are enzymes that promote the hydrolysis and degradation of cAMP. Inhibiting PDE4 enzymes has been studied as an alternative strategy for treating respiratory diseases and autoimmune disorders. This review summarizes the medicinal chemistry research on designing effective PDE4 inhibitors, focusing on their chemical classes, structural aspects, binding properties, inhibitory efficacy, PDE4 selectivity, and therapeutic potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Rheumatology
Eduardo Mysler, Ana Lizarraga
Summary: Upadacitinib and filgotinib, two JAK1 selective drugs, have shown rapid improvements in disease activity, function, and patient reported outcomes in extensive phase III clinical trials for rheumatoid arthritis. With upadacitinib already approved in most markets globally, the studies focused on demonstrating therapeutic efficacy and safety of these drugs in RA treatment.
Article
Rheumatology
Kevin L. Winthrop, Peter Nash, Kunihiro Yamaoka, Eduardo Mysler, Nasser Khan, Heidi S. Camp, Yanna Song, Jessica L. Suboticki, Jeffrey R. Curtis
Summary: In patients with RA, treatment with Upadacitinib (UPA) was associated with higher incidence and event rates of herpes zoster (HZ) compared to treatment with methotrexate (MTX) monotherapy or adalimumab (ADA) + MTX. The risk of HZ was also higher with the 30 mg dose of UPA compared to the 15 mg dose. Patients from Asia and those with a history of HZ may have an increased risk of HZ while receiving UPA.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Immunology
Siyuan Fan, Jiuliang Zhao, Bo Hou, Mange Liu, Jingwen Niu, Yan Zhou, Chenhui Mao, Haitao Ren, Feng Feng, Mengtao Li, Xiaofeng Zeng, Yicheng Zhu, Hongzhi Guan
Summary: The clinical and neuroimaging characteristics of rheumatoid meningitis (RM) in Chinese patients were analyzed retrospectively. Among 933 patients with rheumatoid arthritis (RA), six patients were identified with RM. Headache, hyperacute focal neurological deficits, and seizures were the most common symptoms. Meninges were affected in all patients and cerebral parenchyma in one patient. The lesions were generally located in the frontoparietal region. Immunotherapy, including tocilizumab, showed good response in most patients. RM in Chinese patients share similar characteristics and respond well to immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Hoang Oanh Nguyen, Tiziana Schioppa, Laura Tiberio, Fabrizio Facchinetti, Gino Villetti, Maurizio Civelli, Annalisa Del Prete, Francesca Sozio, Carolina Gaudenzi, Mauro Passari, Ilaria Barbazza, Silvano Sozzani, Valentina Salvi, Daniela Bosisio
Summary: This article reports the research results of an oral PDE4 inhibitor called Tanimilast, which can modulate the pro-inflammatory potential and Th1-polarizing potential of SCV2-RNA-induced DCs. Tanimilast did not affect the expression of maturation markers and lymph node homing receptor in DCs, but skewed towards Th2 phenotype. Both Tanimilast and the reference drug β-methasone blocked the increase of MHC-I molecules in activated DCs and restrained the proliferation and activation of cytotoxic CD8(+) T cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Artur Swierczek, Krzysztof Pociecha, Hanna Plutecka, Marietta Slusarczyk, Grazyna Chlon-Rzepa, Elzbieta Wyska
Summary: In this study, the potential treatment effect of a new theophylline derivative, compound 34, as a phosphodiesterase (PDE)4 and PDE7 inhibitor for autoimmune diseases was evaluated. The results showed that compound 34 displayed high efficacy in animal models of multiple sclerosis, rheumatoid arthritis, and autoimmune hepatitis. Inhibition of PDE types in immune cells may serve as an alternative treatment strategy for autoimmune diseases.
Article
Rheumatology
Daniel H. Solomon, Jon T. Giles, Katherine P. Liao, Paul M. Ridker, Pamela M. Rist, Robert J. Glynn, Rachel Broderick, Fengxin Lu, Meredith T. Murray, Kathleen Vanni, Leah M. Santacroce, Shady Abohashem, Philip M. Robson, Zahi Fayad, Venkatesh Mani, Ahmed Tawakol, Joan Bathon
Summary: This study found that adding either a TNFi or triple therapy led to clinically important improvements in vascular inflammation. However, adding a TNFi did not reduce arterial inflammation more than triple therapy.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Erik Kemper, Nafise Ghalandari, Hetty Wintjes, Anneke Van Steensel-Boon, Laura Kranenburg, Annemarie Mulders, Hubertina Crijns, Hieronymus Smeele, Radboud J. E. M. Dolhain
Summary: The study shows that patients with RA are more likely to breast feed their offspring, which may be attributed to the availability of lactation-compatible medication and pregnancy counseling. The breastfeeding rates among patients with RA are similar to those in the general population.
Review
Rheumatology
Tiago Pecanha, Daniel J. Bannell, Sofia Mendes Sieczkowska, Nicola Goodson, Hamilton Roschel, Victoria S. Sprung, David A. Low
Summary: Physical activity has a beneficial impact on microvascular and macrovascular function in patients with autoimmune rheumatic diseases, but does not show clear effects on macrovascular structure.
Article
Rheumatology
Roy M. Fleischmann, Desiree van der Heijde, Vibeke Strand, Tatsuya Atsumi, Iain B. Mcinnes, Tsutomu Takeuchi, Peter C. Taylor, Marguerite Bracher, David Brooks, John Davies, Christopher Goode, Anubha Gupta, Sumanta Mukherjee, Ciara O'Shea, Didier Saurigny, Lorrie A. Schifano, Celia Shelton, Julia E. Smith, Millie Wang, Reena Wang, Sarah Watts, Michael E. Weinblatt
Summary: This study aimed to investigate the efficacy and safety of otilimab in patients with active rheumatoid arthritis. The results showed that otilimab demonstrated superiority in improving clinical disease activity and reducing disability index, but its efficacy was inferior to tofacitinib.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Jeffrey R. Curtis, Kunihiro Yamaoka, Yi-Hsing Chen, Deepak L. Bhatt, Levent M. Gunay, Naonobu Sugiyama, Carol A. Connell, Cunshan Wang, Joseph Wu, Sujatha Menon, Ivana Vranic, Juan J. Gomez-Reino
Summary: This study evaluated malignancies and their associations with baseline risk factors and cardiovascular risk scores in patients with rheumatoid arthritis (RA) treated with tofacitinib and tumour necrosis factor inhibitors (TNFi). The results showed that the risk of malignancies was increased with tofacitinib compared to TNFi, and the highest incidence was observed in patients with a history of atherosclerotic cardiovascular disease (HxASCVD) or increasing cardiovascular risk.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Vanessa L. Kronzer, Weixing Huang, Paul F. Dellaripa, Sicong Huang, Vivi Feathers, Bing Lu, Christine K. Iannaccone, Ritu R. Gill, Hiroto Hatabu, Mizuki Nishino, Cynthia S. Crowson, John M. Davis, Michael E. Weinblatt, Nancy A. Shadick, Tracy J. Doyle, Jeffrey A. Sparks
Summary: This study identified obesity, high CRP levels, poor functional status, and extensive smoking as novel risk factors for RA-ILD, which may be helpful for RA-ILD risk assessment and prevention. The overall predictive ability for RA-ILD remains modest.
JOURNAL OF RHEUMATOLOGY
(2021)
Article
Rheumatology
Gerd R. Burmester, Peter Nash, Bruce E. Sands, Kim Papp, Lori Stockert, Thomas Jones, Huaming Tan, Ann Madsen, Hernan Valdez, Stanley B. Cohen
Summary: This study analyzed adverse events of special interest in tofacitinib clinical programs across four diseases, finding that infections were the most common adverse events in all diseases. The incidence rates for herpes zoster and serious infections were highest, and the adjusted mortality ratios weighted for country were relatively low across cohorts. The safety profile of tofacitinib was generally consistent across diseases and with longer term follow-up compared to previous analyses.
Article
Rheumatology
Johan Law-Wan, Marc-Antoine Sparfel, Sophie Derolez, Nicolas Azzopardi, Philippe Goupille, Jacqueline Detert, Denis Mulleman, Theodora Bejan-Angoulvant
Summary: In rheumatoid arthritis (RA), patients who are more responsive to TNFi are those who are non-obese, have a longer disease duration, and have a higher initial disease activity. Results from analyzing individual data of 11,617 patients from 29 RCTs highlight the importance of these patient characteristics in predicting responsiveness to TNFi therapy.
Article
Biochemistry & Molecular Biology
Vincenzo Patamia, Giuseppe Floresta, Chiara Zagni, Venerando Pistara, Francesco Punzo, Antonio Rescifina
Summary: In this study, an in silico analysis was conducted on 1,2-dibenzoylhydrazine (DBH) with regards to three essential receptors (EcR, urease, and HIV-integrase). Docking studies were performed based on a crystallographic structural study, revealing that DBH is an outstanding candidate for inhibiting EcR receptors and urease. Additionally, the activity of DBH on HIV integrase receptor was identified, providing a starting point for developing novel inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Vincenzo Patamia, Rosario Tomarchio, Roberto Fiorenza, Chiara Zagni, Salvatore Scire, Giuseppe Floresta, Antonio Rescifina
Summary: Advancements in materials science have led researchers to explore nature for new materials, and in this case, cyclodextrins have been functionalized to improve their CO2 adsorption capacity. These functionalized cyclodextrins showed similar adsorption capacity to BEA zeolite and could also enhance drug adsorption. Characterization techniques such as NMR and mass spectrometry were used to determine the degree of functionalization, and FTIR spectroscopy confirmed the presence and interaction of CO2 adsorbed by the material. In silico studies further supported the chemisorption process observed experimentally.
Article
Biochemistry & Molecular Biology
Yandong Ran, Mohammed Moursy, Robert C. Hider, Agostino Cilibrizzi
Summary: Investigation was made on an aromatic substrate for hydroxylation by hydroxyl radicals ((OH)-O-center dot). The probe, N,N'-(5-nitro-1,3-phenylene)-bis-glutaramide, and its hydroxylated product were found not to bind either iron(III) or iron(II), thus not interfering with the Fenton reaction. A spectrophotometric assay based on the hydroxylation of the substrate was developed, providing univocal and sensitive (OH)-O-center dot detection. The assay demonstrated the lack of Fenton activity of iron(III) complexes of long-chain fatty acids under biological conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Vincenzo Patamia, Chiara Zagni, Ilaria Brullo, Erika Saccullo, Alessandro Coco, Giuseppe Floresta, Antonio Rescifina
Summary: In medical imaging, various techniques such as MRI, contrast-enhanced CT, PET, and SPECT are used for disease diagnosis. Peptide-based PET probes offer advantages over traditional antibody-based tracers, including lower cost and the ability to be radiolabeled with different radionuclides. Computational design approaches are being increasingly used in the design of novel peptide-based radiopharmaceuticals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Rosario Tomarchio, Vincenzo Patamia, Chiara Zagni, Letizia Crocetti, Agostino Cilibrizzi, Giuseppe Floresta, Antonio Rescifina
Summary: Ordinary small molecule de novo drug design is time-consuming and expensive. Computational tools, such as molecular dynamics (MD) simulations and steered molecular dynamics (SMD), have shown promise in accelerating the drug design process. In this paper, we applied SMD to evaluate the binding properties of small molecules with FABP4, which is of interest for inhibiting FABP4 and has therapeutic potential in treating cancer and other diseases.
Article
Virology
Virginia Fuochi, Giuseppe Floresta, Rosalia Emma, Vincenzo Patamia, Massimo Caruso, Chiara Zagni, Federica Ronchi, Celestino Ronchi, Filippo Drago, Antonio Rescifina, Pio Maria Furneri
Summary: It is known that the spike protein of human coronaviruses can bind to a secondary receptor to facilitate the virus entry. This study aims to evaluate the inhibitory activity of heparan sulfate and enoxaparin sodium on viral strains HCoV-229E and HCoV-OC43. In vitro experiments and molecular docking simulations confirmed the interactions at the interface of the spike proteins.
Article
Chemistry, Multidisciplinary
Chiara Zagni, Andrea Antonino Scamporrino, Paolo Maria Riccobene, Giuseppe Floresta, Vincenzo Patamia, Antonio Rescifina, Sabrina Carola Carroccio
Summary: Researchers propose a hybrid system based on pHEMA to actively support a nanocontainer filled with a drug for skin wound healing in space. The material, characterized by chemical-physical methods, demonstrated good swelling ability and can contain up to 5.5 mg of the drug.
Article
Chemistry, Medicinal
Giuseppe Floresta, Letizia Crocetti, Renan Rodrigues de Oliveira Silva, Vincenzo Patamia, Francesca Mazzacuva, Yu Chee Sonia Chen, Claudia Vergelli, Agostino Cilibrizzi
Summary: Current clinical research suggests that fatty acid-binding protein 4 inhibitors (FABP4is) have potential in treating cancer and other illnesses. Optimizing the structure of a series of FABP4is led to the discovery of 14e as the most potent analog with IC50 = 1.57 μM, suggesting it as a potential candidate for further in vivo studies.
ARCHIV DER PHARMAZIE
(2023)
Editorial Material
Pharmacology & Pharmacy
Giuseppe Floresta, Chiara Zagni, Vincenzo Patamia, Antonio Rescifina
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Review
Biochemistry & Molecular Biology
Jian Jin, Francesca Mazzacuva, Letizia Crocetti, Maria Paola Giovannoni, Agostino Cilibrizzi
Summary: Cyclic nucleotide phosphodiesterases 4 (PDE4) are enzymes that promote the hydrolysis and degradation of cAMP. Inhibiting PDE4 enzymes has been studied as an alternative strategy for treating respiratory diseases and autoimmune disorders. This review summarizes the medicinal chemistry research on designing effective PDE4 inhibitors, focusing on their chemical classes, structural aspects, binding properties, inhibitory efficacy, PDE4 selectivity, and therapeutic potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Robert Charles Hider, Charareh Pourzand, Yongmin Ma, Agostino Cilibrizzi
Summary: This article describes the chemical nature of intracellular labile iron pools (LIPs) and suggests that mass spectrometric techniques should be adopted to isolate such species due to the kinetic lability of these pools. It also introduces iron-sensitive fluorescent probes developed for the detection and quantification of LIP, including those designed to monitor cytosolic, mitochondrial, and lysosomal LIPs, and discusses the potential of near-infrared (NIR) probes for in vivo monitoring of LIP.
Article
Chemistry, Multidisciplinary
Chiara Zagni, Alessandro Coco, Sandro Dattilo, Vincenzo Patamia, Giuseppe Floresta, Roberto Fiorenza, Giusy Curcuruto, Tommaso Mecca, Antonio Rescifina
Summary: New polymeric macroporous materials based on poly 2-hydroxyethyl methacrylate (pHEMA) were synthesized and tested for CO2 adsorption. The materials functionalized with lysine and histidine showed exceptional adsorption capacity. The morphology of the materials, specifically hydrogels, played a significant role in improving the adsorption performance.
MATERIALS TODAY CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Mariacristina Failla, Giuseppe Floresta, Vincenzo Abbate
Summary: In medical imaging, techniques such as magnetic resonance imaging, contrast-enhanced computerized tomography, and positron emission tomography (PET) are extensively used for disease diagnosis and treatment. Peptide-based targeting PET probes, which are small peptides with high affinity and specificity to specific cellular and tissue targets, can be easily modified and radiolabelled with various radionuclides, making them attractive for clinical use. This review focuses on recent technologies in synthesizing and radiolabelling peptide PET-based molecular probes with the most commonly used radioisotopes in 2022.
RSC MEDICINAL CHEMISTRY
(2023)
