Search results for "Molecular target"

Role of the IL-23/IL-17 Pathway in Rheumatic Diseases: An Overview

2021

Interleukin-23 (IL-23) is a pro-inflammatory cytokine composed of two subunits, IL-23A (p19) and IL-12/23B (p40), the latter shared with Interleukin-12 (IL-12). IL-23 is mainly produced by macrophages and dendritic cells, in response to exogenous or endogenous signals, and drives the differentiation and activation of T helper 17 (Th17) cells with subsequent production of IL-17A, IL-17F, IL-6, IL-22, and tumor necrosis factor α (TNF-α). Although IL-23 plays a pivotal role in the protective immune response to bacterial and fungal infections, its dysregulation has been shown to exacerbate chronic immune-mediated inflammation. Well-established experimental data support the concept that IL-23/IL…

New Insight into Immunity and Immunopathology of Rickettsial Diseases

2011

Human rickettsial diseases comprise a variety of clinical entities caused by microorganisms belonging to the generaRickettsia,Orientia,Ehrlichia, andAnaplasma. These microorganisms are characterized by a strictly intracellular location which has, for long, impaired their detailed study. In this paper, the critical steps taken by these microorganisms to play their pathogenic roles are discussed in detail on the basis of recent advances in our understanding of molecularRickettsia-host interactions, preferential target cells, virulence mechanisms, three-dimensional structures of bacteria effector proteins, upstream signalling pathways and signal transduction systems, and modulation of gene exp…

Humoral immunotherapy of multiple myeloma: perspectives and perplexities

2010

IMPORTANCE OF THE FIELDS Multiple myeloma (MM) is a hematological malignancy still remaining incurable despite the various therapies available, mainly because of the high fraction of refractory/relapsing cases. Therefore, the development of novel therapeutic approaches is urgently needed to overcome conventional treatment resistance. AREAS COVERED IN THIS REVIEW: In the era of targeted therapies, treatments combining a high specificity for neoplastic cells and the capability to interfere with environmental signals should be regarded as the weapons of choice. Monoclonal antibody (mAb)-based humoral immunotherapy could satisfy both these requirements when applied to MM. Indeed, many of the mo…

New prognostic markers in neuroblastoma

2013

Introduction: The hallmark of neuroblastoma is its clinical and biological heterogeneity, with the likelihood of cure varying widely according to age at diagnosis, extent of disease and tumor biology. We hope this review will be useful for understanding part of the unfamiliar neuroblastoma codex. Areas covered: In the first part of this review, the authors summarize the currently used prognostic factors for risk-adapted therapy, with the focus on clinical management of neuroblastoma patients. In the second part, the authors discuss the evolving prognostic factors for future treatment schemes. A search of online medical research databases was undertaken focusing especially on literature publ…

Targeted synthetic disease-modifying antirheumatic drugs in spondyloarthritis

2017

Therapies in early development for the treatment of opiate addiction.

2015

Opiate drugs are psychoactive substances used to manage severe pain. However, their chronic use is associated with the development of addiction. Opiate addiction represents a significant public health concern.This review focuses on the most recent advances in the pharmacological treatment of opiate addiction, from those being tested in clinical trials (Phase I and II), to preclinical studies that point to new targets. Readers will gain knowledge of the wide variety of treatments used to treat opiate addiction, including their strengths and weaknesses, and the promising pharmacological targets identified by preclinical research.Among the currently available agonist therapies, new dosage form…

Dipeptidyl Enoates As Potent Rhodesain Inhibitors That Display a Dual Mode of Action

2015

Dipeptidyl enoates were prepared through a high-yielding two-step synthetic route. They have a dipeptidic structure with a 4-oxoenoate moiety as a warhead with multiple reactive sites. Dipeptidyl enoates were screened against rhodesain and human cathepsins B and L, and were found to be potent and selective inhibitors of rhodesain. Among them (S,E)-ethyl 5-((S)-2-{[(benzyloxy)carbonyl]amino}-3-phenylpropanamido)-7-methyl-4-oxooct-2-enoate (6) was the most potent, with an IC50 value of 16.4 nm and kinact/Ki=1.6×106 m−1 s−1 against rhodesain. These dipeptidyl enoates display a reversible mode of inhibition at very low concentrations and an irreversible mode at higher concentrations. Inhibition…