Synthesis and biological evaluation of peptide-derived TSLP inhibitors

Choi

et al. 2019

Sci Rep

Self Cite

Thymic stromal lymphopoietin (TSLP) plays an important role in the differentiation and proliferation of Th2 cells, resulting in eosinophilic inflammation and numerous allergic diseases. Baicalein ( 1 ), a major component of Scutellaria baicalensis , was found to be the first small molecule to block TSLP signaling pathways. It inhibited effectively eosinophil infiltration in house dust mite-induced and ovalbumin-challenged mouse models. Structure-activity relationship studies identified compound 11a , a biphenyl flavanone analog, as a novel human TSLP inhibitor for the discovery and development of new anti-allergic drugs.

Section: Introductionmentioning

confidence: 99%

Structure-Activity Relationships of Baicalein and its Analogs as Novel TSLP Inhibitors

Choi

et al. 2019

Sci Rep

Self Cite

“…In a subset of patients with severe asthma, TSLP expression remained enhanced, independent of treatment with high-dose ICS or OCS [ 73 ]. Therefore, targeting TSLP signalling represents an intriguing therapeutic strategy in asthma [ 74 ].…”

Section: Resultsmentioning

confidence: 99%

Investigational Treatments in Phase I and II Clinical Trials: A Systematic Review in Asthma

et al. 2022

Inhaled corticosteroids (ICS) remain the mainstay of asthma treatment, along with bronchodilators serving as control agents in combination with ICS or reliever therapy. Although current pharmacological treatments improve symptom control, health status, and the frequency and severity of exacerbations, they do not really change the natural course of asthma, including disease remission. Considering the highly heterogeneous nature of asthma, there is a strong need for innovative medications that selectively target components of the inflammatory cascade. The aim of this review was to systematically assess current investigational agents in Phase I and II randomised controlled trials (RCTs) over the last five years. Sixteen classes of novel therapeutic options were identified from 19 RCTs. Drugs belonging to different classes, such as the anti-interleukin (IL)-4Rα inhibitors, anti-IL-5 monoclonal antibodies (mAbs), anti-IL-17A mAbs, anti-thymic stromal lymphopoietin (TSLP) mAbs, epithelial sodium channel (ENaC) inhibitors, bifunctional M3 receptor muscarinic antagonists/β2-adrenoceptor agonists (MABAs), and anti-Fel d 1 mAbs, were found to be effective in the treatment of asthma, with lung function being the main assessed outcome across the RCTs. Several novel investigational molecules, particularly biologics, seem promising as future disease-modifying agents; nevertheless, further larger studies are required to confirm positive results from Phase I and II RCTs.

“…In a subset of patients with severe asthma, TSLP expression remains enhanced, independent of treatment with high-dose inhaled or oral corticosteroids [ 116 ]. Therefore, TSLP signalling blockade is a highly promising therapeutic approach for allergic diseases and asthma [ 117 , 118 , 119 ].…”

Section: Overview Of the Pharmacological Anti-tslp Strategiesmentioning

confidence: 99%

Thymic Stromal Lymphopoietin (TSLP), Its Isoforms and the Interplay with the Epithelium in Allergy and Asthma

Smolińska

Antolín‐Amérigo

Popescu

et al. 2023

IJMS

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that has emerged as a critical player in the development and progression of allergy and asthma. It is primarily produced by epithelial cells and functions as a potent immune system activator. TSLP acts through interaction with its receptor complex, composed of the TSLP receptor (TSLPR) and interleukin-7 receptor alpha chain (IL-7Rα), activating downstream complex signalling pathways. The TSLP major isoform, known as long-form TSLP (lfTSLP), is upregulated in the airway epithelium of patients with allergic diseases. More research is warranted to explore the precise mechanisms by which short-form TSLP (sfTSLP) regulates immune responses. Understanding the dynamic interplay between TSLP and the dysfunctional epithelium provides insights into the mechanisms underlying allergy and asthma pathogenesis. Targeting TSLP represents an important therapeutic strategy, as it may upstream disrupt the inflammatory cascade and alleviate symptoms associated with allergic inflammation.