GLAXO/MRS PAPERRoles of chemokines in the regulation of leucocyte recruitment*

2001 ◽  
Vol 100 (4) ◽  
pp. 359-362
Author(s):  
Ian SABROE ◽  
Timothy J. WILLIAMS ◽  
James E. PEASE
Keyword(s):  
Small Molecules ◽  
Inflammatory Disease ◽  
Chemokine Receptors ◽  
Allergic Inflammation ◽  
New Treatments ◽  
Leucocyte Recruitment

In the search for new treatments for human inflammatory disease, antagonism of chemokine receptors by small molecules is an attractive goal. Although there are overlapping patterns of expression of chemokine receptors between leucocyte types, an investigation of the chemokine responsiveness of cells important in allergic inflammation, such as the eosinophil and the basophil, is beginning to uncover how selective recruitment may be regulated. The story of the eotaxin receptor, CCR3, and its central role in allergic inflammation illustrates that therapeutic antagonism of these pathways is imminently achievable.

scholarly journals PET Imaging Radiotracers of Chemokine Receptors

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5174
Author(s):  
Santosh R. Alluri ◽  
Yusuke Higashi ◽  
Kun-Eek Kil
Keyword(s):  
Small Molecules ◽  
Chemokine Receptors ◽  
Brain Disorders ◽  
Infectious Agents ◽  
Cardiovascular Research ◽  
Critical Signal ◽  
Inflammatory Reactions ◽  
Positron Emission

Chemokines and chemokine receptors have been recognized as critical signal components that maintain the physiological functions of various cells, particularly the immune cells. The signals of chemokines/chemokine receptors guide various leukocytes to respond to inflammatory reactions and infectious agents. Many chemokine receptors play supportive roles in the differentiation, proliferation, angiogenesis, and metastasis of diverse tumor cells. In addition, the signaling functions of a few chemokine receptors are associated with cardiac, pulmonary, and brain disorders. Over the years, numerous promising molecules ranging from small molecules to short peptides and antibodies have been developed to study the role of chemokine receptors in healthy states and diseased states. These drug-like candidates are in turn exploited as radiolabeled probes for the imaging of chemokine receptors using noninvasive in vivo imaging, such as positron emission tomography (PET). Recent advances in the development of radiotracers for various chemokine receptors, particularly of CXCR4, CCR2, and CCR5, shed new light on chemokine-related cancer and cardiovascular research and the subsequent drug development. Here, we present the recent progress in PET radiotracer development for imaging of various chemokine receptors.

Chemokines and Chemokine Receptors in Allergic Inflammation

1998 ◽  
pp. 157-167 ◽  
Author(s):  
Marco Baggiolini ◽  
Mariagrazia Uguccioni ◽  
Pius Loetscher
Keyword(s):  
Chemokine Receptors ◽  
Allergic Inflammation

Unravelling the mechanisms underpinning chemokine receptor activation and blockade by small molecules: a fine line between agonism and antagonism?

2007 ◽  
Vol 35 (4) ◽  
pp. 755-759 ◽  
Author(s):  
E. Wise ◽  
J.E. Pease
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Molecular Mechanisms ◽  
Receptor Activation ◽  
G Protein Coupled Receptors ◽  
Considerable Effort ◽  
G Protein Coupled ◽  
Migration Of Cells

Chemokines are a family of small basic proteins which induce the directed migration of cells, notably leucocytes, by binding to specific GPCRs (G-protein-coupled receptors). Both chemokines and their receptors have been implicated in a host of clinically important diseases, leading to the notion that antagonism of the chemokine–chemokine receptor network may be therapeutically advantageous. Consequently, considerable effort has been put into the development of small-molecule antagonists of chemokine receptors and several such compounds have been described in the literature. One curious by-product of this activity has been the description of several small-molecule agonists of the receptors, which are typically discovered following the optimization of lead antagonists. In this review we discuss these findings and conclude that these small-molecule agonists might be exploited to further our understanding of the molecular mechanisms by which chemokine receptors are activated.

Allergic Rhinitis: Manifestations and Response to Treatment

1995 ◽  
Vol 112 (5) ◽  
pp. P93-P93
Author(s):  
Robert M. Naclerio ◽  
Fuad M. Baroody
Keyword(s):  
Allergic Rhinitis ◽  
Side Effects ◽  
Paranasal Sinuses ◽  
Allergic Inflammation ◽  
Upper Airway ◽  
Allergic Patient ◽  
Comprehensive Approach ◽  
Response To Treatment ◽  
Educational Objectives ◽  
New Treatments

Educational objectives: To understand the contribution of allergic inflammation of the upper airway to diseases of the ears, paranasal sinuses, and lungs; to understand available and new treatments for allergic rhinitis, with their side effects and costs; and to formulate a comprehensive approach to the management of the allergic patient.

scholarly journals Nano-chemistry and Bio-conjugation with perspectives on the design of Nano-Immune platforms, vaccines and new combinatorial treatments

2021 ◽  
pp. 049-056
Author(s):  
Gomez Palacios Luna R ◽  
Martinez Sofia ◽  
Tettamanti Cecilia ◽  
Quinteros Daniela ◽  
Bracamonte A Guillermo
Keyword(s):  
Small Molecules ◽  
Mechanisms Of Action ◽  
Chemical Structures ◽  
Functional Nanoparticles ◽  
Corona Virus ◽  
New Treatments

This Mini-Review and Opinion letter, it was addressed different themes and topics implicated in the development of new treatments and vaccines applied to pathologies developed in humans such as by Virus and related pathogens. In this context, it was presented and discussed different strategies used, which were contemplated from the design of small molecules, towards higher sized chemical structures and new Nanoarchitectures. In particular, it was discussed varied studies developed for the Corona Virus treatment; which afforded to the main mechanisms of action of pharmacophores and targeted functional Nanoparticles. In this direction, it was highlighted the importance of Bioconjugation of molecules and variable Nanoarchitectures for their incorporation within cells as well as for the development of Nano-vaccines. Moreover, it was discussed about the development of combinatory treatments based on different strategies recently reported. Similarly, it was presented different studies and developments actually in progress related to the design of functional and Multifunctional Nano-platforms with potential perspectives on Lab-On particles and Nano-vaccines for precision Nanomedicine and new treatments.

Targeted Metabolomic Profiles Are Strongly Correlated With Metabolic Alterations In Patients With Sickle Cell/Beta Thalassemia Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4675-4675 ◽  
Author(s):  
Ioannis Papassotiriou ◽  
Fottes Panetsos ◽  
Theodora Livadara ◽  
Maria Dimopoulou ◽  
Andreas Tzivaras ◽  
...  
Keyword(s):  
Small Molecules ◽  
Sickle Cell ◽  
High Performance ◽  
Conflicts Of Interest ◽  
Beta Thalassemia ◽  
Strongly Correlated ◽  
Comparable Concentration ◽  
New Treatments ◽  
Reticulocyte Production

Background The complex pathophysiology of Sickle Cell Disease (SCD) makes unlikely that a single therapeutic agent will prevent or reverse all SCD complications. Metabolomic analysis might help in the characterization of the endogenous and exogenous effects of potential new treatments. Metabolites are small molecules that are chemically transformed during metabolism and provide a functional readout of cellular state. Metabolites serve as direct signatures of biochemical activity and are therefore easier to correlate with phenotype. The metabolome is typically defined as the collection of small molecules produced by cells and offers a window for interrogating how mechanistic biochemistry relates to cellular phenotype. There are very few reports providing comprehensive measurements of metabolites present in blood and almost no reports on metabolites changes associated with SCD. In this context we aimed to detect and to quantify targeted metabolites’ abnormalities in patients with Sickle Cell/beta thalassemia disease (HbS/βThal) and their implication in pathways that might be of interest to prevent vaso-occlusion and/or to monitor the effects of new therapies on SCD. Patients and Methods Twenty adult patients with HbS/βThal were enrolled in the study, while 20 apparently healthy individuals matched for age served as controls. Targeted metabolome analyses based on aminoacids and carnitines were performed after extraction from dry blood spots (DBSs) on filter paper using High Performance Liquid Chromatography followed by tandem Mass Spectrometry (LC/MS/MS), with derivatization (AB SCIEX 5500 triple quadrupole and QTRAP® LC/MS/MS Systems, Framingham, MA, USA) with reagents provided by Chromsystems Instruments & Chemicals, Germany. The injection volume was 10 µL and the analysis lasted ca. 2 min. Results The main results of the study showed that: a) fifty metabolites were separated in patients and controls samples, b) mapping the results of analyses, patients with HbS/βThal compared to controls had 17 metabolites with significantly lower concentration, 10 metabolites with comparable concentration and 23 metabolites with significantly higher concentration, c) L-arginine and L-ornithine concentrations were significantly lower in patients HbS/βThal compared to controls, 9.3±2.6 vs 14.7±3.7 µmoles/L, (p<0.01), and 116.0±15.0 vs 211.2±19.5 µmoles/L, (p<0.001), respectively, while L-citrulline was lower in patients HbS/βThal compared to controls but no significantly 21.8±2.5 vs 25.1±2.5 µmoles/L, (p>0.06) and d) carnitine, acetylcarnitine and propionylcarnitine correlated significantly positive with reticulocyte production index (p<0.001). Conclusions Our findings showed significant alterations in whole blood metabolome of patients with HbS/βThal. Also we demonstrated the very important metabolic abnormality of Nitric Oxide biosynthesis pathway due to the low concentration of the aminoacids serving of substrates in this cycle and disturbances in carnitine and acylcarnitines homeostasis. These abnormalities in the metabolome reflected the hemolysis, inflammatory process and pulmonary hypertension observed in these patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals New Small Molecule Drugs for Thrombocytopenia: Chemical, Pharmacological, and Therapeutic Use Considerations

2019 ◽  
Vol 20 (12) ◽  
pp. 3013 ◽  
Author(s):  
Page Clemons Bankston ◽  
Rami A. Al-Horani
Keyword(s):  
Small Molecules ◽  
Previous Treatment ◽  
Specific Patient ◽  
Chemical Structures ◽  
Small Molecule Drugs ◽  
Thrombopoietin Receptor ◽  
Insufficient Response ◽  
Syk Inhibitor ◽  
New Treatments ◽  
Orally Active

This review provides details about three small molecules that were recently approved by the FDA for the treatment of thrombocytopenia. The new treatments include lusutrombopag, avatrombopag, and fostamatinib. The first two drugs are orally active thrombopoietin receptor (TPO-R) agonists which are FDA-approved for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. Fostamatinib is orally active prodrug that, after activation, becomes spleen tyrosine kinase (SYK) inhibitor. Fostamatinib is currently used to treat chronic and refractory immune thrombocytopenia in patients who have had insufficient response to previous treatment. Chemical structures, available dosage forms, recommended dosing, pharmacokinetics, results of toxicity studies in animals, most frequent adverse effects, significant outcomes of the corresponding clinical trials, and their use in specific patient populations are thoroughly described. Described also is a comparative summary of the different aspects of five currently available therapies targeting TPO-R or SYK for the treatment of thrombocytopenia.

The Role of Eosinophil Chemokine Receptors in Allergic Inflammation in Vivo

1998 ◽  
Vol 95 (s39) ◽  
pp. 13P-13P
Author(s):  
I Sabroe ◽  
A Hartnell ◽  
D Conroy ◽  
PD Collins ◽  
NP Gerard ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Allergic Inflammation
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